Biopharmaceuticals – Leonid E. Lerner, OcuJect LLC
Abstract for “Intraocular delivery methods and devices”
“Injection devices are used to deliver pharmaceutical compositions into the eyes. A resistance component is used to control the injection of the needle through an eye wall. You can place the resistance component on an attachment to an injector or on a part of the housing. Some devices include a filter to remove air, infectious agents and/or particulate matter before injecting the composition into the eye. The devices may also be used in conjunction with other methods.
Background for “Intraocular delivery methods and devices”
The eye is complex organ that enables sight to occur. The condition of each part and their ability to work together will affect the quality of vision. Conditions that affect the retina, lens, or macula can cause vision problems. These and other conditions have been treated with topical and systemic drug formulas, each with its own drawbacks. Topical treatments that are applied to the eye’s surface have a shorter residence time due to the tear flow, which washes them from the eye. The natural barrier of the cornea and the sclera limits drug delivery to the eye. Additional structures are required if the target is located in the posterior chamber. Systemic treatments often require high dosages of drug to reach therapeutic levels in the eye. This increases the risk for side effects.
“Currently, intravitreal injection devices that are commercially available lack many features to expose the injection site, stabilize the device against the skin, and/or control the depth and angle of injection. Many of the devices in the patent literature (e.g. U.S. 2007/0005016 and WO 2008/084064) are part of multi-component systems, which are often time-consuming to set up. These devices can increase the likelihood of complications due to their longer procedure times. The risk of complications from user error and the need to handle many components at once can increase. Intraocular injection can lead to serious complications, such as intraocular infections, which is also known as endophthalmitis. This happens when pathogenic organisms like bacteria are introduced to the intraocular environment from the ocular surfaces or trauma to the tissues.
“New devices that can perform intravitreal injections are desirable,” says Dr. Xavier. It would be beneficial to have ergonomic devices that make injections easier and less likely to cause complications. It would be helpful to have devices that can accurately and atraumatically inject drugs into the eye, such as liquid, semisolid or suspension-based drugs.
“These devices, methods and systems allow for the delivery of pharmaceutical formulations to the eye. They may also be integrated. Integrated is a synonym for “integrated”. It refers to the combination of different features that can be useful in delivering pharmaceutical formulations into an eye. A single device may include features that help with the placement of the drug formulations on the desired eye surface, position the device to allow access to the intraocular space at the right angle, keep it stable while being inserted, adjust or control intraocular tension, and/or minimize trauma from forceful injections or contact with the eye wall. The integrated devices can be used to minimize trauma from direct contact with target tissue, or indirectly through force transmission through other tissues, such as the vitreous gel or eye wall, as well minimizing trauma to the cornea and intraocular structures, including the retina, choroid, ciliary body and nerves. Other features that can help reduce intraocular infectious inflammation, such as endophthalmitis, and may help to relieve pain could also be included. The pharmaceutical formulations can be delivered to any location in the eye that is suitable, such as the anterior chamber and posterior chamber. The pharmaceutical formulations can contain any active ingredient and take any form. The pharmaceutical formulations can be solid, semi-solid, or liquid. You can also adapt the pharmaceutical formulations to any type of release. They can be modified to release active agents in an instant release, controlled release or delayed release.
“Generally, the devices described here have a housing that can be used with one hand. A typical housing has two ends: a proximal and distal. Contact surface at the housing’s distal end. The housing will normally contain a conduit in its pre-deployed condition. In its deployed state, the conduit will usually be within the housing at least partially. Sometimes, the conduit can be attached to the housing by sliding. The conduit will have a proximal and distal ends, as well as a lumen. The housing may contain an actuation mechanism that can be connected to the conduit or a reservoir. For holding active agent. An actuation mechanism may be activated by a trigger that is attached to the housing. One variation of the device housing has a trigger located near the tip of the device at the ocular contact. This trigger is placed on the side of a device housing, close to the tip of the device. The distance between the trigger tip and the device tip can vary from 5 mm up to 50 mm, 10 mm up to 25 mm or 15 mm down to 20 mm. Another variation has a trigger located on the side housing of the device. This trigger is 90 degrees from a measuring component so that the device tip can be placed perpendicularly to the limbus and activated using the tip of the second or the third finger of that hand. One variation includes a measuring component attached to the ocular contact surfaces. A drug loading mechanism may be included in some variants.
“The actuation mechanism can be either manual, partially automated, or automated. One variation of the actuation system is a spring-loaded mechanism. The mechanism can be either one spring or two springs. Another variation of the actuation mechanism includes a pneumatic actuator mechanism.
“The injection of pressure on the eye’s surface may be achieved by adding a resistance component (e.g., dynamic resistance component) to the injection device. A slidable element may be attached to the housing as a dynamic resistance component. The slidable element may include a dynamic sleeve that adjusts the pressure on the eye surface. The dynamic resistance component can also be used to control the tension in the ocular wall.
“In one variant, the injection device comprises a housing that can be used for manipulating with one hand. The housing has a proximal and distal ends, and a resistance band around the housing. A dynamic resistance component has a proximal and distal ends. There is also a conduit within the housing. This conduit has a lumen and an actuation mechanism.
“In another variation, an injection device has integrated components. It includes a housing that can be used for manipulating with one hand. The housing may have a proximal and distal ends, as well as a sectoral measuring device coupled to the distal end. The circumference of the sectoral measuring component can be circular or periphery. It may also include a core member with a proximal, distal, and circumference. There may also be a plurality radially-extending members. An injection device may include a conduit within the housing. The conduit can have a proximal and distal ends, as well as a lumen. It also has an actuation mechanism that is coupled to the housing.
“Another variation of the injection device is that it may have a housing that can be used for manipulating with one hand. The housing has a wall, a distal and proximal ends, and an ocular. Contact surface at the housing’s distal end. A conduit that is at least partially contained within the housing. The conduit has a proximal and distal ends. There is also a lumen that extends therethrough. An actuation mechanism connected to the housing and operably connected with a reservoir. For holding an agent, a dynamic resistance element, and a filter.
“Reported here are systems for delivering compositions to the eye. These systems could include a housing that is sized and shaped to be used with one hand. The housing may have a proximal and distal ends; and an ocular contact area at the housing’s distal end. The conduit can be at least partially contained within the housing. It may have a distal, proximal, and lumen. A reservoir is typically placed within the housing to hold the active agent. These systems can also contain a variable resistance component that is coupled to the housing distal edge and an air removal mechanism. The air removal mechanism is designed to remove air from composition before it is delivered to the eye.
“Alternatively, systems for delivering compositions into the eye may also include a Syringe Body with a Proximal End and a Distal End, and a Reservoir for the composition. An injector attachment that is removably coupled at the distal end of syringe and has a variable resistance component, may be included. An air removal mechanism may be included in the system. This mechanism removes air from the composition prior to it being delivered into the eye.
The systems described herein could also include a terminal sterilization and/or jet control mechanisms, in addition to an effective air removal mechanism. A hydrophobic filter material with a small pore size may be used as the air removal mechanism. The pore size can range from about 0.01 m to approximately 50 m, or between about 0.01 m and about 10 m. Or from around 0.2 m to just over 5 m. Some variations of the air removal mechanism include a number of hydrophobic filters. An air removal mechanism can be especially beneficial when compositions containing ranibizumab and other viscous substances are injected into the eyes.
“Drug delivery systems can be equipped with an air- or gas-resistance element (e.g. a hydrophilic filter) as well as a vent (e.g. a hydrophobic filter). Hydrophilic filter membranes can increase resistance to gas flow and stop it from passing through drug conduits. They also divert it through a hydrophobic vent and out of the device to facilitate gas or air removal from the drug composition. Gas-resistance resistance and vent components can be located adjacently. The vent and gas-resistance components may also be integrally formed with the drug conduit or needle hub, or provided as separate, attachable/detachable components (with the needle hub or any part of the injection device). The gas-resistance element may be at most partially or fully air-impermeable in any conditions. It can also be impermeable when wetted. The gas-resistance element may block air from the drug composition from entering a drug channel. The vent could be used to provide an anti-airlock or gas (air) removal mechanism. The vent could include an air-release valve, or a hydrophobic Membrane.
The devices are used to deliver drug into the intraocular area by placing an ocular surface of the integrated device on an eye. There is also a reservoir that holds an active agent and an activation mechanism. Pressure against the eye’s surface at the target injection site by using the ocular surface. Finally, the active agent is delivered into the eye through the activation mechanism. All the steps of applying, positioning, and delivering drugs can be done with one hand. A topical anesthetic may be applied to the eye prior to placing the device. Before the device is placed on the eye, an antiseptic can be applied to the eye’s surface.
“The intraocular pressure generated by pressure applied against the eye’s surface using the ocular touch surface can also range between 15 mmHg to 120mm Hg or 20 mmHg to 90mm Hg, 25 mmHg to 60mm Hg. The intraocular pressure generated before the dispensing device is deployed (conduit), may decrease scleral flexibility, facilitate conduit penetration through the sclera during injection procedures, and/or reduce backlash.
The methods include: placing an ocular contact area of an injection device against an eye wall, generating variable resistance for conduit advancement as conduit is deployed through the wall. After the conduit has been deployed through the wall, the composition is removed from the eye using an air removal mechanism. Finally, the composition is injected into the eye. The force needed to cause movement against the resistance generated may range from 5 gm up to 100 gm or 10 gm up to 30 gm. It may take from 20 gm to 25 gm of force, depending on the variation to activate resistance component.
In some cases, the method might include coupling an injection attachment to a Syringe Body, with the injector attachment comprising an adjustable resistance component, an air-removal mechanism, an ocular surface and a needle; placing the ocular surface of the injector attach against the eyewall; creating variable resistance to needle advancement; passing the composition through an air removal mechanism to remove air from the composition; injecting the composition into your eye.
“Drug delivery devices, their components, and/or active agents can be included in systems or kits as separate components. Systems or kits can include injection devices, attachments to injectors and active agents. Preloaded devices or those that can be manually loaded with drugs may be included. Multiple active agents can be included in the device. Different active agents can be used. You can use the same active agent or different doses. Instructions for using the systems or kits are usually included. These kits may contain anesthetic and/or antiseptic drugs.
These devices include methods and systems that deliver pharmaceutical formulations to the eye, including injections. These devices can combine (combine) several features that could be useful in delivering pharmaceutical formulations into an eye. The devices could also be modular. The term “modular” is used herein. A device made from multiple components that can be attached or detached from the housing is called?modular?. For example, e.g., various resistance components, filters (e.g., a hydrophilic and/or hydrophobic filter combination), ocular measuring components, etc., may be configured as attachable/detachable components that can be combined with a syringe housing. Features that aid in proper placement of the eye and help position the intraocular may be included. A single device may include features that allow for space access at the right angle and/or depth. They can also adjust or control the ocular wall tension and/or minimize trauma to the intraocular structures and sclera, such as from the force of injections or penetration of the skin. Disposable devices may be used in their entirety or in part. You may be able to use the devices to remove air, infectious agents and/or particulate matter in formulations before injection. It may be beneficial to remove air from compositions containing ranibizumab and other viscous substances before injecting these compositions into your eye. This reduces the chance of the patient experiencing visual disturbances like floaters.
“I. DEVICES”
“In general, integrated or modular devices are described as having a housing that can be easily manipulated with one hand. Housings typically have a proximal and distal ends, with an ocular contact area at the housing’s distal end. The housing may contain a conduit in its pre-deployed condition. In its deployed state, the conduit may be found within the housing at least partially. The conduit can be attached to the housing in some variants. The conduit will have a proximal and distal ends, as well as a lumen. The housing may contain an actuation mechanism that can be connected to the conduit, as well as a reservoir for holding active agents.
“The cyclic-olefin polymers and their hydrogenation products can be ring-opened heteropolymers cyclic-olefin monmers and other monomers as well as addition homopolymers cyclic-olefin monmers and copolymers cyclic-olefin olimers and other monomers. Monocyclic olefin monmers can also include polycyclic monomers of cyclic-olefin olefins, as well as higher-cyclic compounds. Monocyclic monocyclic monomers can be used to produce homopolymers and copolymers of cyclic-olefin olimers. These monocyclic monomers include cyclopentenes, cyclopentadienes, cyclohexenes, methylcyclohexenes and cyclooctene. Lower-alkyl derivatives of these monocyclic monomers contain, as substituents, 1 to 3 lower Alkyl groups like methyl and/or the ethenethenethenethenethenethenethenethenethenethenethyl groups.
“Examples of the polycyclic olefin monomers are dicyclopentadiene, 2,3-dihydrocyclopentadiene, bicyclo[2,2,1]-hepto-2-ene and derivatives thereof, tricycle[4,3,0,12,5]-3-decene and derivatives thereof, tricyclo[4,4,0,12,5]-3-undecene and derivatives thereof, tetracyclo[4,4,0,12,5,07,10]-3-dodecene and derivatives thereof, pentacyclo[6,5,1,13,6,02,7,09,13 4-pentadecene and derivatives thereof, pentacyclo[7,4,0,12,5,0,08,13,19,12]-3-pentadecene and derivatives thereof, and hexacyclo[6,6,1,13,6,110,13,02,7,09,14]-4-heptadecene and derivatives thereof. Examples of bicyclo[2,2,1]-hepto-2-ene derivatives include 5-methyl-bicyclo[2,2,1]hepto-2-ene, 5-methoxy-bicyclo[2,2,1]-hepto-2-ene, 5-ethylidene-bicyclo[2,2,1]-hepto-2-ene, 5-phenyl-bicyclo[2,2,1]-hepto-2-ene, and 6-methoxycarbonyl-bicyclo[2,2,1-]-hepto-2-ene. Examples of tricyclo[4,3,0,12,5]-3-decene derivatives include 2-methyl-tricyclo[4,3,0,12,5]-3-decene and 5-methyl-tricyclo[4,3,0,12,5]-3-decene. Examples of tetracyclo[4,4,0,12,5]-3-undecene derivatives include 10-methyl-tetracyclo[4,4,0,12,5]-3-undecene, and examples of tricycle[4,3,0,12,5]-3-decene derivatives include 5-methyl-tricyclo[4,3,0,12,5]-3-decene.”
“Examples of tetracyclo[4,4,0,12,5,07,10]-3-dodecene derivatives include 8-ethylidenetetracyclo-[4,4,0,12,5,07,10]-3-dodecene, 8-methyl-tetracyclo-[4,4,0,12?5,07,10]-3-dodecene, 9-methyl-8-methoxy-carbonyl-tetracyclo[4,4,0,125,07.10]-3-dodecene, 5,10-dimethyl-tetracyclo[4,4,0, 12,5,07,10]-3-dodecene. Examples of hexacyclo[6,6,1,13,6,110,1302,7,09,14]-4-heptadecene derivatives include 12-methyl-hexacyclo[6,6,1,13,6,110,13,02,7,09,14]-4-heptadecene and 1,6-dimethyl-hexacyclo[6,6,1,13,6,110,13,02,7,09,14]-4-heptadecene. An addition homopolymer of at minimum one cyclic-olefin monmer or an addition copolymer with at least one cyclic monomer and at most one other olefin is one example of a cyclic polymer. The homopolymer (or copolymer) can be made by polymerizing any of the monomers above and using a well-known catalyst that is soluble in hydrocarbon solvent. This catalyst could include a vanadium or similar compound and an organoaluminum or similar compound (Japanese Patent Application Open (Kokai). HEI 6-157672, Japanese Patent Application Laid-Open (Kokai) No. HEI 543663)
A ring-opened homo or a ring opened copolymer of these monomers is another example of a cyclic-olefin polymer. You can make it by homopolymerizing or copolymerizing above monomers. HEI 6-157672, Japanese Patent Application Laid-Open (Kokai) No. HEI 543663)
“The homopolymer and copolymer could contain unsaturated bonds. A known hydrogenation catalyst can be used to hydrogenize the homopolymer and copolymers. The hydrogenation catalysts include (1) Ziegler-type heterogeneous catalysts, which each contain an organic acid salt or nickel of titanium, cobalt or nickel and an organometal compound lithium, aluminum, or the like; (2) supported catalysts, which each consist of a carrier like carbon or alumina, a platinum metal like palladium, or ruthenium, and (3) catalysts that each contain a complex of one the platinum group metals (Japanese Patent Application Laid Open (Kokai). HEI 6157672.
“In some variants, the device, or at least a portion thereof, is made from a material that contains polypropylene, ethylene, or rubber. Examples of suitable rubber materials include butyl rubbers such as butyl rubber, chlorinated butyl rubber, brominated butyl rubber, and divinylbenzene-copolymerized butyl rubber; conjugated diene rubbers such as polyisoprene rubber (high to low cis-1,4 bond), polybutadiene rubber (high to low cis-1,4 bond), and styrene-butadiene copolymer rubber; and ethylene-propylene-diene terpolymer rubber (EPDM). You can also use crosslinkable rubber materials. This is done by adding additives like a crosslinking agent or a filler and/or reinforcement to the rubber material.
The biocompatible material can be any variety of polymers. Nonlimiting examples of suitable biodegradable polymers include cellulose and ester, polyacrylates (L-tyrosine-derived or free acid), poly(?-hydroxyesters), polyamides, poly(amino acid), polyalkanotes, polyalkylene alkylates, polyalkylene oxylates, polyalkylene succinates, polyanhydrides, polyanhydride esters, polyasprutimic acid, polylactic acid, polybutylene digloclate, poly(caprolactone), poly(caprolactone)/poly(ethylene glycol) copolymers, polycarbone, L-tyrosin-derived polycarbonates, polycyanoacrylates, polydihydropyrans, poly(dioxanone), poly-p-dioxanone, poly(c-caprolactone-dimethyl trimethylene carbonate), poly(esteramide), polyesters, aliphatic polyesters, poly(etherester), polyethylene glycol/poly(orthoester) copolymers, poly(glutarunic acid), poly(glycolic acid), poly(glycolide), poly(glycolide)/poly(ethylene glycol) copolymers, poly(lactide), poly(lactide-co-caprolactone), poly(DL-lactide-co-glycolide), poly(lactide-co-glycolide)/poly(ethylene glycol) copolymers, poly(lactide)poly(ethylene glycol) copolymers, polyphosphazenes, polyphosphesters, polyphophoester urethanes, poly(propylene fumarate-co-ethylene glycol), poly(trimethylene carbone), polytyrosine carbonate, polyurethane, terpolymer (copolymers of glycolide lactide or dimethyltrimethylene carbonate), and combinations, mixtures or copolymers thereof.”
To adjust the properties of polymers or polymer blends, additives can be added. A biocompatible plasticizer, for example, may be added to any polymer mixture to improve its flexibility and/or strength or to give the eye a color contrast. A biocompatible filler may also be used to increase the mechanical strength or rigidity of a section of the device, such as a fiber, particulate, and/or mesh.
“The above-described devices can be made, at least in part by injection molding or compression molding the materials.”
In some cases, it might be advantageous to add a removably attached/integrated viewing and/or magnifying device on the device. To aid in visualizing the injection site and the tip of the device, you can attach a magnifying or illumination source (e.g. LED light) to the device. This improved visualization can help you position the device more accurately and safely at a target area, such as about 3.5mm to 4mm posterior to your corneo-scleral line. It will also prevent complications from intraocular injections like retinal detachment or ciliary body bleeding. You can make the magnifying glass from any material you like, such as any non-resorbable (biodegradable), material. However, the magnifying glasses will be lightweight so it doesn’t affect the balance of your injection device. The magnifying glass, and/or the illumination source (e.g., LED), may be disposable.
“Housing”
The housing contains the drug reservoir and the actuation mechanism. The conduit can be found within the housing in its initial, non-deployed (pre-deployed) state. You can have any shape housing, as long as you are able to grasp and manipulate the housing with one hand. The housing can be rectangular, square or circular in shape, and may also be cylindrical or tubular. Some housings are cylindrical or tubular, similar to the barrel of an syringe. The housing can have a length of about 1 cm to about 15 cm, about 2.5 cm to about 10 cm or approximately 4 cm to 7.5 cm. The housing can have a length between about 1 cm and about 3 cm. It may also be about 4 cm or about 5 cm. It could also be about 6 cm, approximately 7 cm or about 9 cm. It might also have a length about 10 cm., 11 cm., 12 cm., 13 cm., 14 cm., or 15 cm. To aid in the manipulation and gap creation of the housing, the surface may be texturized or roughened. Any of the actuation mechanisms described below may be used with grips. Grips can be used to maintain a steady grip with the device by using two, three, or four fingers. The plunger actuation mechanism may be found on the device housing within close proximity to the grip. It could also be integrated with the grip or within 1.0 mm to 10 mm of it. This allows the operator to use his fingers to slide the actuation handle while keeping a firm grip and maintaining control of the device. The distance the actuation lever can travel is between 2.0 mm to about 8.0mm or between 1.0 mm to about 15 mm. It is important to maintain a steady grip when actuating the drug injector mechanism. This helps to locate the injection site on your eye surface with a precision of about 0.5mm.
“Some housings include a syringe barrel with a distal end that contains a luer. Any type of luer can be used, including slip-tip, lock, or luer snap. If the luer locks type is used, it can interface with a drug conduit through twisting the drug conduit on/off. The luer-snap luer may have a raised edge at the tip of the luer that can interlock with the raised ridge on the hub of a drug channel to form a male/female type connection. Although the luer snap connection can increase the strength of the connection between the housing and the drug conduit (having a reservoir within), it does not have the rigid lock of a luerlock type connection.
“Some versions of the luer?snap connector might provide tactile feedback to verify that the drug conduit is properly positioned and stably connected with the housing. For example, the hub of the drug channel has been placed far enough on the luer to prevent it from slipping during drug injection.”
The luer-snap connector could also include a self-positioning mechanism that ensures the drug conduit hub is positioned correctly on the luer. One ridge may be located on the exterior surface of the luer, while the other ridge may be located inside the drug conduit hub. However, at least one ridge has a steep leading slope and steep trailing slope, which may allow the drug conduit’s self-positioning and snap into place after the ridges are advanced past one another.
“Ocular Contact Surfaces.”
“The devices described in this document generally have an atraumatic optical contact surface at their distal ends. Some variations attach the ocular contact area to the housing’s proximal edge. Other variations of the ocular surface are removable and attached to the housing’s proximal edge. The ocular contact surfaces are usually sterile. Sometimes, the ocular surface can be disposable. The device’s ocular contact surface is placed on the eye during use.
The ocular contact surface can be any size, shape, or geometry as long as it permits atraumatic placing of the device on the surface. Some variations of the ocular contact surfaces are ring-shaped (e.g. FIGS. 1A-1B). The ocular contact surface may be shaped like a ring and have a diameter between 0.3mm and 8mm, 1mm to 6mm, 2mm to 4mm, and 3mm to 6mm. Other variations of the ocular surface include a circular or oval shape.
“More precisely, as shown in FIGS. The device tip is a ring-shaped, ocular contact surface. This means that the distance between the inner and outer diameters of the ring creates a rim. The ring-shaped Ocular Contact Surface may have a larger ocular surface (rim) and a smaller opening (12). 1A), or a narrower ocular surface (14) (rim), with a larger internal opening (16). 1B). 1B. The dispensing member (conduit), may be an injection pen that is concealed inside the device tip and protected by it. You may also have a membrane that runs across the internal opening. It may be flush with the eye’s contact surface, or hidden within the lumen of your device tip.
“As shown at FIGS. 39A-39B: The tip of the dispensing members may be receded relative to the end of the device housing tip comprising ocular contact surfaces in the resting state. This allows the device tip to contact any surface, such as skin or eye walls, by placing it in contact with the surface. 39B. 39B.
“In some variants, the dispensing tip is receded relative to the housing and is separated by the nearest end by a distance of about 0.01 mm up to about 10mm, about 0.1mm to approximately 5 mm or about 0.5mm to around 2 mm.”
An enclosure can be placed on the distal end to protect the dispensing device from contact with eye lashes and eye lids. It also helps to keep it safe from possible contamination. The dispensing device may be extended from the enclosure to penetrate the eye wall, and enter an eye cavity. It is not exposed to any ocular appendages like eyelids or eyelashes harboring bacteria. Intraocular infection is a risky condition because the eye is an immune-privileged body. The dispensing member can be enclosed to prevent it from coming in contact with bacteria-infected ocular appendages. This will reduce the chance of intraocular infection that could cause sight-threatening damage. The sterile enclosure can be configured in one variant using the dynamic sleeve, which is further described below. A membrane may be used to cover the dynamic sleeve so that ocular surface tears cannot enter the orifice at the device tip, potentially contaminating it before it’s deployed.
“In some variations, the outer edge of the device tip may have a raised surface that seals the exit point of the dispensing unit from the tip. Once the device tip is positioned on the eye, the seal can be used to stop ocular tears circulating through the injection site. You can make the raised surface round, square, rectangular or triangular.
“In an alternative variation, the ocular contact area of the device tip that is in direct contact with the eyes is ring-shaped. This means there is a clearance between the internal wall and dispensing member of approximately 360 degrees. These are marked in FIG. 39C. 39C. FIG. 39D shows that there is no clearing around the dispensing members. 39D may lead to accidental infectious contamination at the injection site.
“In some variations there may be a gap between the dispensing member and the device housing. It can range from about 0.01 mm up to 5 mm, from 0.3 mm down to 3 mm or from about 0.25 mm up to 2 mm.
“In other variations, there may be a solid membrane (105) that separates a tip of the dispensing device (107) from the outside environment. FIG. 39E. The membrane or partition can be either water-impermeable or air-impermeable. The membrane or partition can seal the device and maintain a constant air pressure.
“Furthermore the membrane or partition may prevent the tip of the dispensing device from coming in contact with any accidental bacterial contamination, such as tears, ocular secretions, or other sources of bacteria prior to the injection procedure. This minimizes the risk for accidental bacterial contamination and reduces the risk of intraocular infection. Endophthalmitis can be caused by injections.
“The membrane or partition that separates the tip of the dispensing member from the end of the device housing may comprise a material selected from the group consisting of biocompatible and non-biodegradable materials including without limitation, methylmethacrylate (MMA), polymethylmethacrylate (PMMA), polyethylmethacrylate (PEM), and other acrylic-based polymers; polyolefins such as polypropylene and polyethylene; vinyl acetates; polyvinylchlorides; polyurethanes; polyvinylpyrollidones; 2-pyrrolidones; polyacrylonitrile butadiene; polycarbonates; polyamides; fluoropolymers such as polytetrafluoroethylene (e.g., TEFLON? Polymer; or fluorinated Ethylene Propylene (FEP); polystyrenes, styrene butadiene-styrenes; cellulose; polymethylpentenes; polysulfoness; polyesters.
“In some cases, the membrane (30) may be recessed within the device tip. This allows the device tip to contact any surface like the skin or eye surface. The membrane or partition can then be separated from that surface using a distance marked by arrows. 39E. 39E.
“The membrane/partition may be receded relative to the end of the device housing at ocular interface by a distance of about 0.01 mm or about 10 mm. It can also be separated from the end of that housing by about 0.1mm or about 5 mm. Or, it could be removed from the end with a distance of about 0.5mm or about 2 mm.
“In further variations, a measuring part (32) may be recessed relative the end of device housing (33) at ocular contact surface (FIGS. 39F-39H, so that the device tip (34) touches the eye surface (35)(FIG. 39I, the measuring component (32) is not in direct contact with the eye surface (35). This arrangement may reduce the chance of injury to delicate tissue on the eye surface, such as the conjunctiva and non-keratinizing epithelia. It may be advantageous to avoid direct contact between the measuring instrument and the eye surface. This reduces the chance of corneal or conjunctival trauma. Alternate options include angled or directed tip (32) of the measuring instrument. 39G and 39H are the respective versions. You can place the measuring component in a recess relative to the housing’s end by approximately 0.01 mm to 5 mm, 0.01 to 3 mm or 0.5 mm up to 2 mm.
“Some variations are shown in FIGS. “In some variations, as shown in FIGS. 2A-2C,” the device tip may also include a ring-shaped contact surface and a measuring instrument that help to determine the location of the injection site at a specific distance relative to and perpendicular the corneoscleral limbus. One variation of the device tip has the measuring component (20), located on one side (22). Another variation allows for more than one measuring element to be located on the tip of the device. The tip of the measuring part is flat in this example (FIG. 2C and does not protrude significantly above the ocular contact surface. Other variations include raising the tip of the measuring device (FIGS. 2A-2B) is raised above the ocular surface. This allows it to keep the eyelids from sliding over the top and bottom of the measuring component. This may help reduce intraocular infections and accidental contamination during injections.
“In other variations, a flange is used to contact the ocular surface (e.g. FIGS. 3A1-3A3, FIGS. 3B1-3B3, FIG. FIG. 4B1-4B2). 4B1-4B2). The pressure force per unit area at the interface may be reduced, which could reduce the risk of conjunctival injury by the device tip pressing against the eye wall. It is important to avoid conjunctival injury because the conjunctiva has delicate, non-keratinizing epithelium that contains multiple sensory nerve endings.
“In some cases, the flange may be curved so that the eye lid can travel over the top and along the ocular surface. However, it prevents the lid from touching the sterile ocular touch surface of the device tip. You may also find FIGS. 4A and 4B1-4B2 that the ocular contact surface can be a ring-shaped Flange. 4A, 4B1-4B2. This flange could also be used to prevent the eyelid from coming into contact with the sterile ocular contact surface at the device tip.
“More precisely, as shown at FIG. 3), the edge of the flange could be thin (FIG. 3A1) allows the eyelid to slide over the flange and contact the shaft of device tip. Alternately, the flange can be thicker (FIG. 3B1) to prevent the eyelid from sliding across it and keep it from coming into contact with the shaft. This will prevent inadvertent contamination. If the device tip’s flange is thick at the ocular contact, the edges of its edges may be rounded to protect the delicate, non-keratinizing epithelium that is rich in nerve endings or pain receptors. Alternate versions of the device tip may have a flat ocular contact interface (FIGS). 3A1 to 3B1, convex (FIGS), 3A2 and3B2, or concave. 3A3 and 3B3 are used to decrease the risk of injury to the ocular surface tissues, such as the conjunctiva. They also provide a way to apply a force on the eyewall and increase intraocular pressure to facilitate needle penetration. FIGS. FIGS.
“In further variations, the contact surface of the eye may be convex, concave or concave (e.g. FIGS. 5, 7). FIGS. FIGS. 5A1-5A2 show a device tip with a flat ocular contact area. Alternately, the device tip can have a protruding ocular contact surface or convex one (FIGS). 5B1-5B2, which can improve contact between the inner opening of the device tips and the ocular surface. This may reduce the risk of eye wall indentation when the device tip is pressed against a wall. Another variation is to have the device tip’s ocular contact surface indented or concave. This reduces the chance of injury to the conjunctiva and other ocular tissue. These configurations of the device tip’s ocular contact surface may decrease the risk of accidental damage to the ocular surface tissues such as the conjunctiva. They also provide a way to apply pressure to the eye wall and increase the intraocular pressure to facilitate needle penetration through it.
“More precisely, as shown at FIG. 7), the ocular contact surface can be perpendicular to its long axis (FIGS. 7A1-7A2 or flat and slanted relative the long-axis device (7B1-7B2), or convex and perpendicular the long-axis device (FIG. 7C1 or is convex, slanted relative the long axis (FIG. 7C2 or is round (FIG. 7D), or is oval. (FIG. 7E). One variation of the ocular interface can be rounded or oval (e.g. similar to 7E). The tip of a Qtip. The thickness of the contact surface can be between 0.01mm and 10mm, from about0.05mm to around 5mm, or from about 1 mm up to 2 mm.
One or more features, such as slip-reducing features, may be included in the ocular contact surfaces to help stabilize them on the eye surface. This helps prevent slippage. One variation of the Ocular Contact Surface may include one or more traction elements. These features could be bumps, ridges, raised details, etc. that increase the surface traction of the contact surface on the eye without being abrasive. This ocular contact surface can provide a medium-, high-, or strong-traction interface that stabilizes the device tip on the eye’s surface and prevents it from moving during intraocular drugs delivery. Another variation of the ocular surface is one that includes an adhesive interface, such as a suction mechanism. Variation in the material used to make an ocular contact surface can help to prevent slippage.
The materials used to create the ocular contact surfaces may help prevent irritation, scratching, and abrasion of the eye surface. Exemplary non-abrasive materials that may be employed include without limitation, nylon fiber, cotton fiber, hydrogels, spongiform materials, Styrofoam materials, other foam-like materials, silicone, plastics, PMMA, polypropylene, polyethylene, fluorinated ethylene propylene (FEP), and polytetrafluoroethylene (PTFE). When making contact with the eye, thermoplastic elastomers (e.g. silicone) may be useful. These materials can be either semi-hard or hard and can be used to prevent conjunctival abrasion or subconjunctival bleeding during transcleral needle deployment or any other accidental trauma to the ocular surfaces (FIG. 6). The durometer of an ocular contact surface material may range from 30 A to 60 A. These materials may also be used in contact lens manufacturing.”
“In certain variations, the edges on the ocular contact surfaces are also rounded to protect the tissues beneath the conjunctiva. This is because the conjunctiva is covered with delicate epithelium rich nerve endings and pain receptors. FIG. 6 The ocular contact surface could have a circumference that corresponds to the device tip’s circumference (FIGS. 6A1-6A2). Other variations may see the ocular contact surface protruding beyond the circumference the shaft of a device tip. This creates a flange (FIGS. 6B1-6B2). 6B1-6B2.
The ocular contact surface can also be flexible or deformable and conforms to the eye’s surface when it is placed against the eye during intraocular drug delivery. The eye’s surface that is in direct contact with said interface surface includes, but not limited to: the area of the eye covering the parsplana region, which is defined as the area around the limbus and the corneoscleral limbal. This area covers the area from about 2 to 7 mm past and around the limbus. An interface surface that conforms with the curvature on the eye’s surface may allow for the creation of an optimal contact interface between device and eye. This may help to ensure the safety of injection procedures and sterility in intraocular drug delivery. Ocular interface materials are materials that can conform to the eye’s surface (which is usually deformable or flexible) and in particular to the curvature at the pars plana, which is located about 2-5mm posterior to intravitreal drug application. Materials that are not abrasive to corneal epithelium and non-keratinizing conjunctival may be used. The materials and their configurations include foam, braid, knits, weave, fiber bundle, etc. These materials may be able to form medium- or high-traction surfaces (e.g. hydro gels or cotton), which enable the immobilization of eye globes during injection.
“In some cases, the material comprising the ocular contacts surface may change its properties when it comes into contact with fluid. This could include a reduction in its traction coefficient, such as in cotton fiber. This can reduce the risk of conjunctival damage from contact between the ocular surface and the eye surface. Other variations of the ocular contact surfaces do not experience any changes in their physical or chemical properties when they are exposed to fluids that cover the eye surface, such as tears.
“The ocular contacts surfaces may help to prevent conjunctival or episcleral bleeding when intraocular needle injection is performed. A device with a ring-shaped interface can be used to press against the eye wall. This pressure will then apply pressure to the episcleral and conjunctival vessels, reducing blood flow. The risk of subconjunctival bleeding may be decreased due to the reduced blood flow through these vessels. After intraocular drug application is completed, the needle can be withdrawn. However, the ring-shaped tip of the needle may still be pressed against the wall of the eye. This applies continuous pressure to the episcleral and conjunctival vessels, further reducing or minimising the risk of bleeding.
“In some variants, the device includes an ocular contact area that acts as a drug reservoir. The ocular contact surface can be coated with a drug or incorporated into it. The drug can then be diffused, leaked, or absorbed onto the eye’s surface via the ocular surface. Hydro gels and their derivatives are excellent materials for including drugs.
“Intraocular Pressure Control Mechanisms, Ocular Wall Tension Control Methods”
Controlling intraocular pressure (IOP), during drug delivery procedures, such as intravitreal injection or intraocular injection, can be helpful. Limiting intraocular pressure (or conduit) before dispensing the dispensing member may help to reduce scleral flexibility. This may in turn decrease the unpleasant sensation on the eye’s surface during injections and/or prevent backlash. Backlash is a term that refers to the inability of the conduit to penetrate the eye wall. Backlash is a term that refers to the inability to smooth penetrate the eye wall. This is usually due to scleral flexibility and elasticity. The devices described here may contain one or more IOP control mechanism, also known as ocular tension control mechanisms. Because intraocular pressure is a factor that determines ocular tension, it is also a factor that affects ocular wall strain. Wall tension can also be affected by scleral thickness or rigidity. These factors may vary depending on patient age, gender, and individual variations.
The IOP mechanisms can control IOP during placement and positioning the device tip at the target area on the ocular surface and/or intraocular and intravitreal positioning the dispensing member (conduit), during intraocular and intravitreal injections of a drug. The IOP mechanisms can control IOP before and during intraocular or intravitreal positioning a dispensing device member used for trans-scleral, trans-corneal penetration. IOP will decrease once the dispensing members have penetrated the ocular surface. The dispensing member may penetrate the ocular surface and cause a decrease in IOP.
“Some variations of the IOP control mechanisms enable the devices to generate an IOP of between 15 and 120mm Hg during placement and positioning the device tip at a target area on the ocular surface and/or intraocular positioning. Other variations of the IOP control mechanism allow the devices to generate an IOP of between 20 and 90mm Hg during placement and positioning the device tip at a target spot on the ocular surface and/or intraocular positioning. The IOP control mechanisms can be used to enable the devices to generate an IOP of between 25-60 mm Hg when the device tip is placed at a target spot on the ocular surface and/or intraocular positioning.
The IOP control mechanisms can also be used to keep the IOP between 10 – 120 mm Hg or between 15 – 90 mm Hg or between 20 -60 mmHg for any length of time during intraocular injections. The device may slow down or stop the drug injection rate if the intraocular pressure is higher than a predetermined value. For example, 120 mm Hg or 60 mmHg or 40 mmHg. The IOP control mechanism can be used to detect an IOP level, such as 90 mmHg or 60 mmHg or 40 mmHg during intraocular drug administration.
The IOP control mechanism can include a spring or a mechanical or electrical control mechanism. The IOP control mechanism is designed to balance fluid injection resistance pressure and frictional forces in the injection plunger. This is the force required to push fluid through a needle into pressurized eye fluids. The IOP control mechanisms can be connected to the device housing and actuation system in a way that allows for automatic adjustment of force of dispensing member deployment or advancement. The IOP control mechanism can be programmed to adjust the force of dispensing members and intraocular pressure levels. The IOP control mechanisms can be used to generate a higher IOP than the resting IOP before dispensing member deployment. This is to decrease scleral elasticity and reduce the risk of device backlash and facilitate dispensing members’ scleral penetration.
“In one variant, the IOP control valve is a pressure relief mechanism that bypasses an injection stream when a maximum pressure has been reached. Another variation of the IOP control mechanism is a pressure accumulation that dampens IOP within a defined range. The IOP control mechanism can include a pressure sensor in some variations. Another variation of the IOP control mechanism is a sliding cap or shield. This covers the dispensing unit prior to deployment. However, it may slide along the housing’s surface to expose, deploy or advance the dispensing members, e.g. after reaching a predetermined IOP level. The cap can be adjusted manually, such as with a dial, or it may be automatically adjustable, either step-wise or incrementally. FIG. FIG. 40 shows an example of integrated injection device 500. It includes a cap (502), stop (504), trigger (506), spring (508), plunger (508), seal (512), drug reservoir (514), needle (516) and a syringe (518) among others. When cap (502 is placed on the ocular surface with pressure applied, the cap (502) retracts proximally in the direction of the Arrow to stop (504), and the syringe (518), and needle (516), are advanced. To inject drug from the drug reservoir (514), through needle (516), trigger (506), e.g. a lever, can be depressed. Cap (502) is then placed over the needle (516).
A locking mechanism can also be used to stop the cap, cover, or ocular contact surface from sliding or prevent the dispensing device’s deployment until a predetermined IOP has been reached. If a predetermined IOP has not been reached, the locking mechanism can be used to stop sliding of the cover, cap, or ocular surface. The locking mechanisms on the devices discussed here, which include a sliding cover, cap, or other type of cover, can be released manually, or automatically, when the IOP reaches a preset level. For example, 20 mm Hg to 80 mmHg. These locking mechanisms include, without limitation, high-traction surfaces, locking pins and interlocking raisedridges. Any other locking mechanism that prevents a device’s tip, e.g. the cover or cap, from sliding out of reach of the needle, may also be used.
“In further variations, IOP control mechanisms include a high-traction surface, or raised ridges, on the cap, cover or shield, or ocular touch surface, over the dispensing device member. These features can be found on the inner surface the cap, cover or shield or ocular touch surface. They are designed so that when the dispensing member is moved in the proximal direction, any corresponding structures (e.g. crimps or dimples, protrusions or other raised ridges on the device housing) will mate with the raised ridges to provide resistance to the cap, cover or shield against the eye wall (thereby increasing the ocular wall tension or IOP). As described below, the IOP control mechanism includes a resistance component. As mentioned above, the cap or cover, shield or ocular contact surface can be designed so that sliding can be manually or automatically adjusted, either step-wise or incrementally. Any number of raised ridges may be used. They can be any size, shape and geometries. The raised ridges can be placed in the cover, cap, or ocular contact surface. Sometimes, raised ridges may be configured with sloped surfaces. The distal surface might be more steep than the proximal. This design allows for incremental sliding and incremental increases in IOP. The cap, cover or shield may be slid proximally. However, the decreased slope of proximal’s ridge surface may allow for sliding the cap, cover or shield back over the dispensing device.
When the shield is pushed onto the eye wall, the IOP control mechanisms may slip and expose the needle. The intraocular pressure may be between 10 mm and 150 mmHg, about 12 mm and about 120 mmHg, about 15 and 60 mmHg, or about 15 and 40 mmHg depending on the force exerted.
“Resistance Component”
“The injection of pressure on the surface of the eyes may be achieved by adding a resistance component (e.g., a dynamic resist component) to the injection device. The injection device may allow the dynamic resistance component to be detached from it. The housing may have a dynamic resistance component that includes a sliding element or a partially rotatable element (e.g. rotate 360 degrees) and a fully (or partially) rotatable element (e.g. rotate less than 360 degrees). The device’s dynamic resistance component can be designed so it can be rotated around the long axis using one finger (e.g. the middle finger), while being held with the thumb or index finger of the other hand. The slidable element may include a dynamic sleeve that adjusts the pressure on the eye surface. Certain variations of the ocular-wall tension control mechanism can also function as dynamic resistance elements, as previously mentioned. To initiate the movement of the slidable element against the resistance generated by the sliding elements, a force between 5 gm and about 00 gm (or about 10 gm-about 30 gm) may be required. It may take from 20 gm to 25 gm for the slidable elements to move in some variations. Other variations may require from 3 gm to 30 gm force to move the slidable resistance element.
The dynamic resistance component can also be used as a dynamic sleeves. The dynamic sleeve can be used to increase intraocular pressure or tension before needle injections, similar to the slidable caps. The dynamic sleeve can be manually adjusted to adjust the pressure on the surface of the eyes and thus the tension in the eyewall. The ability to adjust the pressure manually may enable the injector to improve control over the injection site location and angle. It also allows the user to position the device more accurately on the ocular surface before needle deployment. The dynamic sleeve allows the user to position the device tip precisely on the eye surface. They can also press the tip against the wall to increase intraocular pressure and wall tension. You can use the dynamic sleeve to increase intraocular pressure, as described above. The terms “dynamic sleeve” and “sleeve” are interchangeable. ?sleeve,? ?slidable sleeve,? ?dynamic sleeves resistance control mechanism? ?sleeve resistance control mechanism,? They are interchangeable throughout. Some variations of the dynamic sleeve are removable or easily detached from the drug conduit. This leaves the drug conduit entirely exposed. Other variations of the dynamic sleeve are fixed to the drug conduit and cover at least part of the conduit. The dynamic sleeve can be either rigid or non-deformable in further variations. A dynamic sleeve can be designed so that, when a pulling force (e.g. retraction away form the eye) is applied to the sleeve this movement may facilitate needle access and reduce the pressure force (down down to 0 Newton) (??N? Refers to the unit force,?Newton? To slide the sleeve back, the needle must be exposed by applying pressure to the eye wall. A dynamic sleeve can also be designed so that when a pushing force (e.g. advancement) is applied to the sleeve this movement may counteract and prevent needle exposure. This may allow the device tip or the device to apply more pressure to the eyewall prior to the initiation sleeve movement.
“Some versions of the dynamic sleeves provide a variable force that follows an U-shaped curve as described in Example 1 or FIG. 46. This is where the most resistance occurs. There is less resistance between the end and start of dynamic sleeves movement along the housing. This means that the needle will have a high resistance phase upon placement on the eyewall. Then, the resistance to sleeve movement is decreased during needle advancement into eye cavity. The needle will be fully deployed when the dynamic sleeve is at the end its travel path. This will result in increased resistance. The sleeve can come to a gradual, smooth stop instead of abruptly stopping at the end point. This reduces the chance of damaging the inert eye walls and minimizing the risk of discomforting or injuring the eye. An example dynamic sleeve might be tapered at both the distal and proximal ends. FIG. 42. The integrated injection device (42), includes a housing (44), resistance band (46) which is either entirely or partially around the housing and a dynamic sleeves (48), that can slide forward and backwards upon the housing (44) The resistance band that surrounds the housing is sometimes called a resistance strip. The tapered ends of the dynamic sleeves (48) have a proximal (50) as well as a distal (not shown). The tapered ends can provide greater traction along the device housing (44), which is where needle deployment begins and ends. The taper at its proximal (50) is more effective in providing traction and resistance when the dynamic sleeve moves towards the resistance band (46). You can adjust the amount resistance you desire by changing the thickness of the resistance bands (46) The resistance band’s thickness can be adjusted to adjust the amount of resistance desired. It may vary in thickness from 0.01 mm up to 5 mm or from 0.1 mm down to 1 mm. The resistance band’s thickness can be as low as 0.05 mm. It could also range from 0.01 mm to about 5 mm. The width of resistance bands can also vary. It may be as wide as 1.0 mm or 1.5 mm. About 2.5 mm. about 3.0mm. about 3.5mm. about 4.0mm. about 4.5mm. or 5.0mm. The wider middle segment (52) will result in lower-traction and resistance movement. This is followed by higher resistance and traction at the end needle deployment due to the taper at distal end. The dynamic sleeve gradually tapers at the distal ends, producing more traction against the housing until it eventually stops. In some cases, the tapered ends may not be both the distal and proximal ends of the dynamic sleeves.
Components such as circular raised bands and ridges at the tip of the device may provide variable traction. These components can provide counter-traction when they are compared to another circular raised band, ridge or ridge on a movable dynamic sleeves (inner bands and ridges). The outer and inner bands, or ridges, that come into contact with one another before dynamic sleeves move generate high traction. The raised band on one side of the device housing may move past the raised band inside the dynamic sleeves. This can cause a rapid decrease of resistance to dynamic sleeves movement, and therefore less pressure on the eyewall by the device tip. The resistance decrease will be determined by the shape of the interlocking bands and ridges. The profile of resistance decrease can be sine-shaped, for example.
“The resistance component can also be coaxially mounted with the housing and have a lumen and an interior surface that form a step or platform around at least some of it. Some variations of the slidable barrier shield have the platform or step circumnavigating the entire lumen. To provide greater friction (resistance), the shield slides along its housing’s luminal diameter, the platform or step generally reduces the shield’s lumen. The internal diameter of the slidable cover may be smaller in the distal than the proximal. The platform or raised step’s width can range from 0.1 to 5 mm or 0.5 to 2 mm. A raised platform or step may have at least one sloped or rounded edge. This could be either the distal or proximal edge. A raised platform or step may also have an edge that is gradually sloped in order to increase the lumen diameter and reduce friction when the shield slides to expose the needle. The edge can be slopped so that the lumen is larger in the proximal than the distal part of the shield.
Another variation is that the force generated by the dynamic sleeves may decrease from its highest point prior to needle deployment (when it completely covers the needle), down to its lowest point, when the dynamic sleeves begins to move and expose the needle tip. This force stays low until needle deployment and the end of dynamic sleeves travel. This curve of resistance may be a sine-shaped one.
Slideable advancement of a dynamic sleeve can generate resistance forces against its movement that range from 0 N up to about 2N. In other instances, it may generate a force of about 0.1 N to approximately 1 N. The force required to move the sleeves may range from 3 gm to 30 gm.
The resistance component can be attached to an injector attachment, or to an injector assembly that is easily removed from any suitable syringe. This includes syringes with luer lock or luer slip types. The injector attachment’s resistance component may interface with either the external or internal surfaces of a sliding sleeve. Some injector attachments include a disc-shaped or ring-shaped component. This is usually raised above the surface and surrounds at least part of the injector attachment’s exterior. The ring can be used as a handle or grip to manipulate the injector attachment. FIGS. FIGS.
“In certain cases, the resistance component may contain a number of appendages attached or formed as part the needle hub. The device could be designed to have an injector attachment, which can be used to replace the normal loading needle. An injector attachment could include a sterile injection tool (e.g. a 30-33 gauge needle) or a resistance component (e.g. a dynamic sleeve). This modular design has the advantage that drug can be loaded as a regular syringe, so side loading is not necessary. A universal female connector may be included in such a modular assembly. It might include a flange at the attachment’s proximal end. The female connector can allow the injector attachment (i.e. attach and detach) to be removably interfaced with a male-luer-tip drug storage reservoir. A syringe may have a drug reservoir that has a luer fitting for the luer Jock, luer slip configuration or any derivative of the tip. Modular design allows for loading a drug reservoir into any of these devices with a drug vial or container. To transfer the drug from the vial into the reservoir, a loading needle is first needed. You can then remove the loading needle or switch it for an injector attachment.
“For example, see FIG. 53 shows an example injector attachment (1500). The injector attachment (1500), includes a needle hub (11502) that allows for the removal of the attachment (1500). The needle hub (1502) can be configured with multiple projections (1504) that extend distally beyond the needle hub. The figure shows four projections, but you can use any number of projections to the needle hub. You can use six projections or two projections. Any suitable material can be used to make the projections. The projections can be made from any suitable material. One variation of the projections is made from polypropylene. You can also have the projections radially placed around the hub’s periphery in any way you like. The projections can be placed in any way you like, including equally spaced or unevenly spaced. They may also be symmetrically or asymmetrically spaced around the hub’s periphery. The slidable shield (1506) may cover the projections (1504) and needle hub (1502), or may be operatively connected to an ocular contact surface with a measuring component (1508). The projections provide friction (resistance), with the internal surface. You may need to overcome the desired resistive force to advance the resistance (e.g. the slidable Shield) by varying between about 0.01 grams and 100 grams or between about 5.0 grams and 30 grams. FIG. 59. Other friction profiles may also be considered, which could require constant force, increasing force, or a combination of both. You can adjust or optimize the amount of friction by changing the material comprising the contact surfaces, such as by increasing the contact surface or narrowing the slidable-shield lumen’s internal diameter. There may be an interference fit between the projections and the slidable screen in some cases. The interference fit can vary from 0.05 mm to about 1.0mm (about 0.04inches) or from 0.08mm to 0.0.003inches to 0.76mm (about 0.03inches). An interference fit of 0.13mm (about 0.005 in) between the inner diameter (inside diameter), of the slidable cover and the outer diameter (outer diameter) of the needle hub assembly could result in a range of resistance force of approximately 3 to 30 grams. A 2% to 5% interference is sufficient to provide adequate resistance. The interference will be greater the more flexible (i.e. less rigid) the projections. To facilitate smooth sliding, either or both of the contact surfaces can be lubricated or coated. One variation is to place a smooth mobility element (e.g., silicone or thermoplastic-elastomeric washer) inside the shield to create smooth sliding with the drug conduit, the internal surface lumen of shield, or to apply a coating (e.g. a fluoropolymer coat or a lubricant to at least one friction/traction area).
However, shield (1506) movement may not be blocked by all of the projections (1504) You can use any number of projections (1504) to provide resistance. One or two projections from four could be used to provide resistance. Non-resistance projections may be used to provide sliding limits for shields, such as forward and rearward. They may also stop the shield rotating relative to its axis. Attached to the hub (1502) is the needle (1514). It extends distally from there. The force curves, decreases of resistance and amount of force generated by the projections and slidable shield could be identical or similar to those described for dynamic sleeves.
The internal surface of the slidable sleeves may have one or more longitudinal grooves. The grooves can extend through the wall of the sleeves, whether it is full thickness or partial. The grooves prevent the sleeve spinning or rotating around its long axis by allowing the projections of the hub (or needle assembly) to travel within the grooves. The grooves that prevent the sleeve from rotating may be used when the circumference of the tip is 360 degrees. This means that the measuring component does not need to rotate in order to point the measuring part towards the limbus.
The needle can be attached to a hub with multiple projections. A shield, such as the one in FIGS. You can slide the shield 54B or 54C over the needle hub until it snaps into place. The shield is secured to the needle hub using no adhesives. To prevent the shield from moving forward and backward, a safety clip may be attached to your needle hub. Any suitable material can be used to make the needle hub. The needle hub may be made of polypropylene in some cases. Other variations of the needle hub are made from polypropylene. You can also make the slidable shield from any material. The slidable shield can be made of a polycarbonate or polished polycarbonate.
Some safety clips create resistance that hinders shield movement relative to drug conduit. The clip may lock the shield in a specific position or multiple positions (pre-deployment resting place, post-injection ending position, or both) and prevent it from moving relative to the drug conduit. One variation of the safety clip is that it does not rotate relative the device’s long axis. Another example is that the safety clip can be rotated relative to the device’s long axis.
FIGS. 54A-54C. 54A-54C. The injection device (1600), is shown in these figures as consisting of a syringe (1604) with a proximal and distal ends (1606). The distal end (1606) can be removably connected to an injector attachment (1608). This variation is illustrated in FIGS. 54B and 54C: Injector attachment (1608) includes an injector hub (1610) with a proximal and distal ends (1611), 1612 and 4 projections (1614). Any number of projections can be used, as stated previously. The projections (1614), can be configured, shaped and so on. At their distal ends, a tab (1616) is placed. The distal ends can be made with hooks, flaps or tabs instead of tabs. The injector attachment (1608), also includes a sliding shield (1618), with a proximal and distal ends (1620) and slots (1624) that are provided through or partially through the shield (1618). Slots can be any size, shape or geometry and are designed to interact with the slots in a complementary manner. The projections (1614), generally have a slight interference fit to the inside of the slidable Shield (1618). A distal end (1622), of the shield (1618) can have an ocular contact surface with a measuring component (1626). The projections (1614), which slide along the shield’s inside surface (1618), provide resistance to shield (1618). The shield (1618) provides resistance until the projections (1614), reach the slots (1624). The tabs (1616), at the distal ends (1614), expand (e.g. radially expand), into the slots (1624), decreasing resistance to movement of shield (1618). You can adjust the resistance by changing the thickness of tabs and the interference between the projections and the shield’s inner surface. To prevent axial movement of shield (1618) along outer surface (1610) of needle hub (1610), a clip (1607), may be attached to the hub (1610). The clip (1607), which can be removed, can prevent the shield (1618 from moving axially). Clips may be used to prevent the resistance component (e.g. the slidable shield) from moving longitudinally along the device’s axis. Any configuration of the clip is possible that will prevent axial movement of shields when they are coupled to the needle hub. However, it can allow for axial movement when the needle bub is removed. Some variations of the clip can be secured to the housing of the device or the needle hub assembly, so it doesn’t rotate around the housing (e.g. about the longitudinal axis). Other variations may allow the clip to rotate around the housing. As described further below, in some cases, a locking mechanism such as a clip that controls mobility of the dynamic shield/sleeve may be non-removable attached to the housing, shield, needle hub/assembly or drug reservoir or any other part of the device. The locking mechanism can be released by pressing the rear lever. This will release the sliding shield and make it mobile.
Clips that attach to the injector device’s portion or attachment can also be used. Clips can be made in any configuration to prevent the resistance component from moving. You can attach some clips to the housing of your device, while others may be attached to a section of the needle assembly. FIG. The clip could be a lever (6002) attached to the needle assembly (6044) of the device (6000). Lever 6002 has two ends. One end contains a release tab (6006) while the other end has a locking shoulder (608). FIG. 63B) The locking shoulder (6008) touches a portion the resistance mechanism (shown as 6010) to stop the movement of the 6010 slidable sleeves (6010) The release tab (6006) should be depressed in the direction shown in FIGS. 63C-63D: When the release tab (6006) is depressed, the lever (6002) pivots at the point of fixation to needle assembly (6004) so the end with locking shoulder (6008) can be lifted, e.g. in the direction indicated by arrow B. Lifting the locking shoulder (6088) will remove contact between the locking shoulder (6068) and the slidable sleeves (6010) and the slidable shoulder (6010) will allow the slidable shoulder (6010) to slide proximally. The slidable sleeves (6010) can be again locked against movement after injection is completed. Press the locking shoulder (6008) until it touches the slidable sleeves (6010)
Summary for “Intraocular delivery methods and devices”
The eye is complex organ that enables sight to occur. The condition of each part and their ability to work together will affect the quality of vision. Conditions that affect the retina, lens, or macula can cause vision problems. These and other conditions have been treated with topical and systemic drug formulas, each with its own drawbacks. Topical treatments that are applied to the eye’s surface have a shorter residence time due to the tear flow, which washes them from the eye. The natural barrier of the cornea and the sclera limits drug delivery to the eye. Additional structures are required if the target is located in the posterior chamber. Systemic treatments often require high dosages of drug to reach therapeutic levels in the eye. This increases the risk for side effects.
“Currently, intravitreal injection devices that are commercially available lack many features to expose the injection site, stabilize the device against the skin, and/or control the depth and angle of injection. Many of the devices in the patent literature (e.g. U.S. 2007/0005016 and WO 2008/084064) are part of multi-component systems, which are often time-consuming to set up. These devices can increase the likelihood of complications due to their longer procedure times. The risk of complications from user error and the need to handle many components at once can increase. Intraocular injection can lead to serious complications, such as intraocular infections, which is also known as endophthalmitis. This happens when pathogenic organisms like bacteria are introduced to the intraocular environment from the ocular surfaces or trauma to the tissues.
“New devices that can perform intravitreal injections are desirable,” says Dr. Xavier. It would be beneficial to have ergonomic devices that make injections easier and less likely to cause complications. It would be helpful to have devices that can accurately and atraumatically inject drugs into the eye, such as liquid, semisolid or suspension-based drugs.
“These devices, methods and systems allow for the delivery of pharmaceutical formulations to the eye. They may also be integrated. Integrated is a synonym for “integrated”. It refers to the combination of different features that can be useful in delivering pharmaceutical formulations into an eye. A single device may include features that help with the placement of the drug formulations on the desired eye surface, position the device to allow access to the intraocular space at the right angle, keep it stable while being inserted, adjust or control intraocular tension, and/or minimize trauma from forceful injections or contact with the eye wall. The integrated devices can be used to minimize trauma from direct contact with target tissue, or indirectly through force transmission through other tissues, such as the vitreous gel or eye wall, as well minimizing trauma to the cornea and intraocular structures, including the retina, choroid, ciliary body and nerves. Other features that can help reduce intraocular infectious inflammation, such as endophthalmitis, and may help to relieve pain could also be included. The pharmaceutical formulations can be delivered to any location in the eye that is suitable, such as the anterior chamber and posterior chamber. The pharmaceutical formulations can contain any active ingredient and take any form. The pharmaceutical formulations can be solid, semi-solid, or liquid. You can also adapt the pharmaceutical formulations to any type of release. They can be modified to release active agents in an instant release, controlled release or delayed release.
“Generally, the devices described here have a housing that can be used with one hand. A typical housing has two ends: a proximal and distal. Contact surface at the housing’s distal end. The housing will normally contain a conduit in its pre-deployed condition. In its deployed state, the conduit will usually be within the housing at least partially. Sometimes, the conduit can be attached to the housing by sliding. The conduit will have a proximal and distal ends, as well as a lumen. The housing may contain an actuation mechanism that can be connected to the conduit or a reservoir. For holding active agent. An actuation mechanism may be activated by a trigger that is attached to the housing. One variation of the device housing has a trigger located near the tip of the device at the ocular contact. This trigger is placed on the side of a device housing, close to the tip of the device. The distance between the trigger tip and the device tip can vary from 5 mm up to 50 mm, 10 mm up to 25 mm or 15 mm down to 20 mm. Another variation has a trigger located on the side housing of the device. This trigger is 90 degrees from a measuring component so that the device tip can be placed perpendicularly to the limbus and activated using the tip of the second or the third finger of that hand. One variation includes a measuring component attached to the ocular contact surfaces. A drug loading mechanism may be included in some variants.
“The actuation mechanism can be either manual, partially automated, or automated. One variation of the actuation system is a spring-loaded mechanism. The mechanism can be either one spring or two springs. Another variation of the actuation mechanism includes a pneumatic actuator mechanism.
“The injection of pressure on the eye’s surface may be achieved by adding a resistance component (e.g., dynamic resistance component) to the injection device. A slidable element may be attached to the housing as a dynamic resistance component. The slidable element may include a dynamic sleeve that adjusts the pressure on the eye surface. The dynamic resistance component can also be used to control the tension in the ocular wall.
“In one variant, the injection device comprises a housing that can be used for manipulating with one hand. The housing has a proximal and distal ends, and a resistance band around the housing. A dynamic resistance component has a proximal and distal ends. There is also a conduit within the housing. This conduit has a lumen and an actuation mechanism.
“In another variation, an injection device has integrated components. It includes a housing that can be used for manipulating with one hand. The housing may have a proximal and distal ends, as well as a sectoral measuring device coupled to the distal end. The circumference of the sectoral measuring component can be circular or periphery. It may also include a core member with a proximal, distal, and circumference. There may also be a plurality radially-extending members. An injection device may include a conduit within the housing. The conduit can have a proximal and distal ends, as well as a lumen. It also has an actuation mechanism that is coupled to the housing.
“Another variation of the injection device is that it may have a housing that can be used for manipulating with one hand. The housing has a wall, a distal and proximal ends, and an ocular. Contact surface at the housing’s distal end. A conduit that is at least partially contained within the housing. The conduit has a proximal and distal ends. There is also a lumen that extends therethrough. An actuation mechanism connected to the housing and operably connected with a reservoir. For holding an agent, a dynamic resistance element, and a filter.
“Reported here are systems for delivering compositions to the eye. These systems could include a housing that is sized and shaped to be used with one hand. The housing may have a proximal and distal ends; and an ocular contact area at the housing’s distal end. The conduit can be at least partially contained within the housing. It may have a distal, proximal, and lumen. A reservoir is typically placed within the housing to hold the active agent. These systems can also contain a variable resistance component that is coupled to the housing distal edge and an air removal mechanism. The air removal mechanism is designed to remove air from composition before it is delivered to the eye.
“Alternatively, systems for delivering compositions into the eye may also include a Syringe Body with a Proximal End and a Distal End, and a Reservoir for the composition. An injector attachment that is removably coupled at the distal end of syringe and has a variable resistance component, may be included. An air removal mechanism may be included in the system. This mechanism removes air from the composition prior to it being delivered into the eye.
The systems described herein could also include a terminal sterilization and/or jet control mechanisms, in addition to an effective air removal mechanism. A hydrophobic filter material with a small pore size may be used as the air removal mechanism. The pore size can range from about 0.01 m to approximately 50 m, or between about 0.01 m and about 10 m. Or from around 0.2 m to just over 5 m. Some variations of the air removal mechanism include a number of hydrophobic filters. An air removal mechanism can be especially beneficial when compositions containing ranibizumab and other viscous substances are injected into the eyes.
“Drug delivery systems can be equipped with an air- or gas-resistance element (e.g. a hydrophilic filter) as well as a vent (e.g. a hydrophobic filter). Hydrophilic filter membranes can increase resistance to gas flow and stop it from passing through drug conduits. They also divert it through a hydrophobic vent and out of the device to facilitate gas or air removal from the drug composition. Gas-resistance resistance and vent components can be located adjacently. The vent and gas-resistance components may also be integrally formed with the drug conduit or needle hub, or provided as separate, attachable/detachable components (with the needle hub or any part of the injection device). The gas-resistance element may be at most partially or fully air-impermeable in any conditions. It can also be impermeable when wetted. The gas-resistance element may block air from the drug composition from entering a drug channel. The vent could be used to provide an anti-airlock or gas (air) removal mechanism. The vent could include an air-release valve, or a hydrophobic Membrane.
The devices are used to deliver drug into the intraocular area by placing an ocular surface of the integrated device on an eye. There is also a reservoir that holds an active agent and an activation mechanism. Pressure against the eye’s surface at the target injection site by using the ocular surface. Finally, the active agent is delivered into the eye through the activation mechanism. All the steps of applying, positioning, and delivering drugs can be done with one hand. A topical anesthetic may be applied to the eye prior to placing the device. Before the device is placed on the eye, an antiseptic can be applied to the eye’s surface.
“The intraocular pressure generated by pressure applied against the eye’s surface using the ocular touch surface can also range between 15 mmHg to 120mm Hg or 20 mmHg to 90mm Hg, 25 mmHg to 60mm Hg. The intraocular pressure generated before the dispensing device is deployed (conduit), may decrease scleral flexibility, facilitate conduit penetration through the sclera during injection procedures, and/or reduce backlash.
The methods include: placing an ocular contact area of an injection device against an eye wall, generating variable resistance for conduit advancement as conduit is deployed through the wall. After the conduit has been deployed through the wall, the composition is removed from the eye using an air removal mechanism. Finally, the composition is injected into the eye. The force needed to cause movement against the resistance generated may range from 5 gm up to 100 gm or 10 gm up to 30 gm. It may take from 20 gm to 25 gm of force, depending on the variation to activate resistance component.
In some cases, the method might include coupling an injection attachment to a Syringe Body, with the injector attachment comprising an adjustable resistance component, an air-removal mechanism, an ocular surface and a needle; placing the ocular surface of the injector attach against the eyewall; creating variable resistance to needle advancement; passing the composition through an air removal mechanism to remove air from the composition; injecting the composition into your eye.
“Drug delivery devices, their components, and/or active agents can be included in systems or kits as separate components. Systems or kits can include injection devices, attachments to injectors and active agents. Preloaded devices or those that can be manually loaded with drugs may be included. Multiple active agents can be included in the device. Different active agents can be used. You can use the same active agent or different doses. Instructions for using the systems or kits are usually included. These kits may contain anesthetic and/or antiseptic drugs.
These devices include methods and systems that deliver pharmaceutical formulations to the eye, including injections. These devices can combine (combine) several features that could be useful in delivering pharmaceutical formulations into an eye. The devices could also be modular. The term “modular” is used herein. A device made from multiple components that can be attached or detached from the housing is called?modular?. For example, e.g., various resistance components, filters (e.g., a hydrophilic and/or hydrophobic filter combination), ocular measuring components, etc., may be configured as attachable/detachable components that can be combined with a syringe housing. Features that aid in proper placement of the eye and help position the intraocular may be included. A single device may include features that allow for space access at the right angle and/or depth. They can also adjust or control the ocular wall tension and/or minimize trauma to the intraocular structures and sclera, such as from the force of injections or penetration of the skin. Disposable devices may be used in their entirety or in part. You may be able to use the devices to remove air, infectious agents and/or particulate matter in formulations before injection. It may be beneficial to remove air from compositions containing ranibizumab and other viscous substances before injecting these compositions into your eye. This reduces the chance of the patient experiencing visual disturbances like floaters.
“I. DEVICES”
“In general, integrated or modular devices are described as having a housing that can be easily manipulated with one hand. Housings typically have a proximal and distal ends, with an ocular contact area at the housing’s distal end. The housing may contain a conduit in its pre-deployed condition. In its deployed state, the conduit may be found within the housing at least partially. The conduit can be attached to the housing in some variants. The conduit will have a proximal and distal ends, as well as a lumen. The housing may contain an actuation mechanism that can be connected to the conduit, as well as a reservoir for holding active agents.
“The cyclic-olefin polymers and their hydrogenation products can be ring-opened heteropolymers cyclic-olefin monmers and other monomers as well as addition homopolymers cyclic-olefin monmers and copolymers cyclic-olefin olimers and other monomers. Monocyclic olefin monmers can also include polycyclic monomers of cyclic-olefin olefins, as well as higher-cyclic compounds. Monocyclic monocyclic monomers can be used to produce homopolymers and copolymers of cyclic-olefin olimers. These monocyclic monomers include cyclopentenes, cyclopentadienes, cyclohexenes, methylcyclohexenes and cyclooctene. Lower-alkyl derivatives of these monocyclic monomers contain, as substituents, 1 to 3 lower Alkyl groups like methyl and/or the ethenethenethenethenethenethenethenethenethenethenethyl groups.
“Examples of the polycyclic olefin monomers are dicyclopentadiene, 2,3-dihydrocyclopentadiene, bicyclo[2,2,1]-hepto-2-ene and derivatives thereof, tricycle[4,3,0,12,5]-3-decene and derivatives thereof, tricyclo[4,4,0,12,5]-3-undecene and derivatives thereof, tetracyclo[4,4,0,12,5,07,10]-3-dodecene and derivatives thereof, pentacyclo[6,5,1,13,6,02,7,09,13 4-pentadecene and derivatives thereof, pentacyclo[7,4,0,12,5,0,08,13,19,12]-3-pentadecene and derivatives thereof, and hexacyclo[6,6,1,13,6,110,13,02,7,09,14]-4-heptadecene and derivatives thereof. Examples of bicyclo[2,2,1]-hepto-2-ene derivatives include 5-methyl-bicyclo[2,2,1]hepto-2-ene, 5-methoxy-bicyclo[2,2,1]-hepto-2-ene, 5-ethylidene-bicyclo[2,2,1]-hepto-2-ene, 5-phenyl-bicyclo[2,2,1]-hepto-2-ene, and 6-methoxycarbonyl-bicyclo[2,2,1-]-hepto-2-ene. Examples of tricyclo[4,3,0,12,5]-3-decene derivatives include 2-methyl-tricyclo[4,3,0,12,5]-3-decene and 5-methyl-tricyclo[4,3,0,12,5]-3-decene. Examples of tetracyclo[4,4,0,12,5]-3-undecene derivatives include 10-methyl-tetracyclo[4,4,0,12,5]-3-undecene, and examples of tricycle[4,3,0,12,5]-3-decene derivatives include 5-methyl-tricyclo[4,3,0,12,5]-3-decene.”
“Examples of tetracyclo[4,4,0,12,5,07,10]-3-dodecene derivatives include 8-ethylidenetetracyclo-[4,4,0,12,5,07,10]-3-dodecene, 8-methyl-tetracyclo-[4,4,0,12?5,07,10]-3-dodecene, 9-methyl-8-methoxy-carbonyl-tetracyclo[4,4,0,125,07.10]-3-dodecene, 5,10-dimethyl-tetracyclo[4,4,0, 12,5,07,10]-3-dodecene. Examples of hexacyclo[6,6,1,13,6,110,1302,7,09,14]-4-heptadecene derivatives include 12-methyl-hexacyclo[6,6,1,13,6,110,13,02,7,09,14]-4-heptadecene and 1,6-dimethyl-hexacyclo[6,6,1,13,6,110,13,02,7,09,14]-4-heptadecene. An addition homopolymer of at minimum one cyclic-olefin monmer or an addition copolymer with at least one cyclic monomer and at most one other olefin is one example of a cyclic polymer. The homopolymer (or copolymer) can be made by polymerizing any of the monomers above and using a well-known catalyst that is soluble in hydrocarbon solvent. This catalyst could include a vanadium or similar compound and an organoaluminum or similar compound (Japanese Patent Application Open (Kokai). HEI 6-157672, Japanese Patent Application Laid-Open (Kokai) No. HEI 543663)
A ring-opened homo or a ring opened copolymer of these monomers is another example of a cyclic-olefin polymer. You can make it by homopolymerizing or copolymerizing above monomers. HEI 6-157672, Japanese Patent Application Laid-Open (Kokai) No. HEI 543663)
“The homopolymer and copolymer could contain unsaturated bonds. A known hydrogenation catalyst can be used to hydrogenize the homopolymer and copolymers. The hydrogenation catalysts include (1) Ziegler-type heterogeneous catalysts, which each contain an organic acid salt or nickel of titanium, cobalt or nickel and an organometal compound lithium, aluminum, or the like; (2) supported catalysts, which each consist of a carrier like carbon or alumina, a platinum metal like palladium, or ruthenium, and (3) catalysts that each contain a complex of one the platinum group metals (Japanese Patent Application Laid Open (Kokai). HEI 6157672.
“In some variants, the device, or at least a portion thereof, is made from a material that contains polypropylene, ethylene, or rubber. Examples of suitable rubber materials include butyl rubbers such as butyl rubber, chlorinated butyl rubber, brominated butyl rubber, and divinylbenzene-copolymerized butyl rubber; conjugated diene rubbers such as polyisoprene rubber (high to low cis-1,4 bond), polybutadiene rubber (high to low cis-1,4 bond), and styrene-butadiene copolymer rubber; and ethylene-propylene-diene terpolymer rubber (EPDM). You can also use crosslinkable rubber materials. This is done by adding additives like a crosslinking agent or a filler and/or reinforcement to the rubber material.
The biocompatible material can be any variety of polymers. Nonlimiting examples of suitable biodegradable polymers include cellulose and ester, polyacrylates (L-tyrosine-derived or free acid), poly(?-hydroxyesters), polyamides, poly(amino acid), polyalkanotes, polyalkylene alkylates, polyalkylene oxylates, polyalkylene succinates, polyanhydrides, polyanhydride esters, polyasprutimic acid, polylactic acid, polybutylene digloclate, poly(caprolactone), poly(caprolactone)/poly(ethylene glycol) copolymers, polycarbone, L-tyrosin-derived polycarbonates, polycyanoacrylates, polydihydropyrans, poly(dioxanone), poly-p-dioxanone, poly(c-caprolactone-dimethyl trimethylene carbonate), poly(esteramide), polyesters, aliphatic polyesters, poly(etherester), polyethylene glycol/poly(orthoester) copolymers, poly(glutarunic acid), poly(glycolic acid), poly(glycolide), poly(glycolide)/poly(ethylene glycol) copolymers, poly(lactide), poly(lactide-co-caprolactone), poly(DL-lactide-co-glycolide), poly(lactide-co-glycolide)/poly(ethylene glycol) copolymers, poly(lactide)poly(ethylene glycol) copolymers, polyphosphazenes, polyphosphesters, polyphophoester urethanes, poly(propylene fumarate-co-ethylene glycol), poly(trimethylene carbone), polytyrosine carbonate, polyurethane, terpolymer (copolymers of glycolide lactide or dimethyltrimethylene carbonate), and combinations, mixtures or copolymers thereof.”
To adjust the properties of polymers or polymer blends, additives can be added. A biocompatible plasticizer, for example, may be added to any polymer mixture to improve its flexibility and/or strength or to give the eye a color contrast. A biocompatible filler may also be used to increase the mechanical strength or rigidity of a section of the device, such as a fiber, particulate, and/or mesh.
“The above-described devices can be made, at least in part by injection molding or compression molding the materials.”
In some cases, it might be advantageous to add a removably attached/integrated viewing and/or magnifying device on the device. To aid in visualizing the injection site and the tip of the device, you can attach a magnifying or illumination source (e.g. LED light) to the device. This improved visualization can help you position the device more accurately and safely at a target area, such as about 3.5mm to 4mm posterior to your corneo-scleral line. It will also prevent complications from intraocular injections like retinal detachment or ciliary body bleeding. You can make the magnifying glass from any material you like, such as any non-resorbable (biodegradable), material. However, the magnifying glasses will be lightweight so it doesn’t affect the balance of your injection device. The magnifying glass, and/or the illumination source (e.g., LED), may be disposable.
“Housing”
The housing contains the drug reservoir and the actuation mechanism. The conduit can be found within the housing in its initial, non-deployed (pre-deployed) state. You can have any shape housing, as long as you are able to grasp and manipulate the housing with one hand. The housing can be rectangular, square or circular in shape, and may also be cylindrical or tubular. Some housings are cylindrical or tubular, similar to the barrel of an syringe. The housing can have a length of about 1 cm to about 15 cm, about 2.5 cm to about 10 cm or approximately 4 cm to 7.5 cm. The housing can have a length between about 1 cm and about 3 cm. It may also be about 4 cm or about 5 cm. It could also be about 6 cm, approximately 7 cm or about 9 cm. It might also have a length about 10 cm., 11 cm., 12 cm., 13 cm., 14 cm., or 15 cm. To aid in the manipulation and gap creation of the housing, the surface may be texturized or roughened. Any of the actuation mechanisms described below may be used with grips. Grips can be used to maintain a steady grip with the device by using two, three, or four fingers. The plunger actuation mechanism may be found on the device housing within close proximity to the grip. It could also be integrated with the grip or within 1.0 mm to 10 mm of it. This allows the operator to use his fingers to slide the actuation handle while keeping a firm grip and maintaining control of the device. The distance the actuation lever can travel is between 2.0 mm to about 8.0mm or between 1.0 mm to about 15 mm. It is important to maintain a steady grip when actuating the drug injector mechanism. This helps to locate the injection site on your eye surface with a precision of about 0.5mm.
“Some housings include a syringe barrel with a distal end that contains a luer. Any type of luer can be used, including slip-tip, lock, or luer snap. If the luer locks type is used, it can interface with a drug conduit through twisting the drug conduit on/off. The luer-snap luer may have a raised edge at the tip of the luer that can interlock with the raised ridge on the hub of a drug channel to form a male/female type connection. Although the luer snap connection can increase the strength of the connection between the housing and the drug conduit (having a reservoir within), it does not have the rigid lock of a luerlock type connection.
“Some versions of the luer?snap connector might provide tactile feedback to verify that the drug conduit is properly positioned and stably connected with the housing. For example, the hub of the drug channel has been placed far enough on the luer to prevent it from slipping during drug injection.”
The luer-snap connector could also include a self-positioning mechanism that ensures the drug conduit hub is positioned correctly on the luer. One ridge may be located on the exterior surface of the luer, while the other ridge may be located inside the drug conduit hub. However, at least one ridge has a steep leading slope and steep trailing slope, which may allow the drug conduit’s self-positioning and snap into place after the ridges are advanced past one another.
“Ocular Contact Surfaces.”
“The devices described in this document generally have an atraumatic optical contact surface at their distal ends. Some variations attach the ocular contact area to the housing’s proximal edge. Other variations of the ocular surface are removable and attached to the housing’s proximal edge. The ocular contact surfaces are usually sterile. Sometimes, the ocular surface can be disposable. The device’s ocular contact surface is placed on the eye during use.
The ocular contact surface can be any size, shape, or geometry as long as it permits atraumatic placing of the device on the surface. Some variations of the ocular contact surfaces are ring-shaped (e.g. FIGS. 1A-1B). The ocular contact surface may be shaped like a ring and have a diameter between 0.3mm and 8mm, 1mm to 6mm, 2mm to 4mm, and 3mm to 6mm. Other variations of the ocular surface include a circular or oval shape.
“More precisely, as shown in FIGS. The device tip is a ring-shaped, ocular contact surface. This means that the distance between the inner and outer diameters of the ring creates a rim. The ring-shaped Ocular Contact Surface may have a larger ocular surface (rim) and a smaller opening (12). 1A), or a narrower ocular surface (14) (rim), with a larger internal opening (16). 1B). 1B. The dispensing member (conduit), may be an injection pen that is concealed inside the device tip and protected by it. You may also have a membrane that runs across the internal opening. It may be flush with the eye’s contact surface, or hidden within the lumen of your device tip.
“As shown at FIGS. 39A-39B: The tip of the dispensing members may be receded relative to the end of the device housing tip comprising ocular contact surfaces in the resting state. This allows the device tip to contact any surface, such as skin or eye walls, by placing it in contact with the surface. 39B. 39B.
“In some variants, the dispensing tip is receded relative to the housing and is separated by the nearest end by a distance of about 0.01 mm up to about 10mm, about 0.1mm to approximately 5 mm or about 0.5mm to around 2 mm.”
An enclosure can be placed on the distal end to protect the dispensing device from contact with eye lashes and eye lids. It also helps to keep it safe from possible contamination. The dispensing device may be extended from the enclosure to penetrate the eye wall, and enter an eye cavity. It is not exposed to any ocular appendages like eyelids or eyelashes harboring bacteria. Intraocular infection is a risky condition because the eye is an immune-privileged body. The dispensing member can be enclosed to prevent it from coming in contact with bacteria-infected ocular appendages. This will reduce the chance of intraocular infection that could cause sight-threatening damage. The sterile enclosure can be configured in one variant using the dynamic sleeve, which is further described below. A membrane may be used to cover the dynamic sleeve so that ocular surface tears cannot enter the orifice at the device tip, potentially contaminating it before it’s deployed.
“In some variations, the outer edge of the device tip may have a raised surface that seals the exit point of the dispensing unit from the tip. Once the device tip is positioned on the eye, the seal can be used to stop ocular tears circulating through the injection site. You can make the raised surface round, square, rectangular or triangular.
“In an alternative variation, the ocular contact area of the device tip that is in direct contact with the eyes is ring-shaped. This means there is a clearance between the internal wall and dispensing member of approximately 360 degrees. These are marked in FIG. 39C. 39C. FIG. 39D shows that there is no clearing around the dispensing members. 39D may lead to accidental infectious contamination at the injection site.
“In some variations there may be a gap between the dispensing member and the device housing. It can range from about 0.01 mm up to 5 mm, from 0.3 mm down to 3 mm or from about 0.25 mm up to 2 mm.
“In other variations, there may be a solid membrane (105) that separates a tip of the dispensing device (107) from the outside environment. FIG. 39E. The membrane or partition can be either water-impermeable or air-impermeable. The membrane or partition can seal the device and maintain a constant air pressure.
“Furthermore the membrane or partition may prevent the tip of the dispensing device from coming in contact with any accidental bacterial contamination, such as tears, ocular secretions, or other sources of bacteria prior to the injection procedure. This minimizes the risk for accidental bacterial contamination and reduces the risk of intraocular infection. Endophthalmitis can be caused by injections.
“The membrane or partition that separates the tip of the dispensing member from the end of the device housing may comprise a material selected from the group consisting of biocompatible and non-biodegradable materials including without limitation, methylmethacrylate (MMA), polymethylmethacrylate (PMMA), polyethylmethacrylate (PEM), and other acrylic-based polymers; polyolefins such as polypropylene and polyethylene; vinyl acetates; polyvinylchlorides; polyurethanes; polyvinylpyrollidones; 2-pyrrolidones; polyacrylonitrile butadiene; polycarbonates; polyamides; fluoropolymers such as polytetrafluoroethylene (e.g., TEFLON? Polymer; or fluorinated Ethylene Propylene (FEP); polystyrenes, styrene butadiene-styrenes; cellulose; polymethylpentenes; polysulfoness; polyesters.
“In some cases, the membrane (30) may be recessed within the device tip. This allows the device tip to contact any surface like the skin or eye surface. The membrane or partition can then be separated from that surface using a distance marked by arrows. 39E. 39E.
“The membrane/partition may be receded relative to the end of the device housing at ocular interface by a distance of about 0.01 mm or about 10 mm. It can also be separated from the end of that housing by about 0.1mm or about 5 mm. Or, it could be removed from the end with a distance of about 0.5mm or about 2 mm.
“In further variations, a measuring part (32) may be recessed relative the end of device housing (33) at ocular contact surface (FIGS. 39F-39H, so that the device tip (34) touches the eye surface (35)(FIG. 39I, the measuring component (32) is not in direct contact with the eye surface (35). This arrangement may reduce the chance of injury to delicate tissue on the eye surface, such as the conjunctiva and non-keratinizing epithelia. It may be advantageous to avoid direct contact between the measuring instrument and the eye surface. This reduces the chance of corneal or conjunctival trauma. Alternate options include angled or directed tip (32) of the measuring instrument. 39G and 39H are the respective versions. You can place the measuring component in a recess relative to the housing’s end by approximately 0.01 mm to 5 mm, 0.01 to 3 mm or 0.5 mm up to 2 mm.
“Some variations are shown in FIGS. “In some variations, as shown in FIGS. 2A-2C,” the device tip may also include a ring-shaped contact surface and a measuring instrument that help to determine the location of the injection site at a specific distance relative to and perpendicular the corneoscleral limbus. One variation of the device tip has the measuring component (20), located on one side (22). Another variation allows for more than one measuring element to be located on the tip of the device. The tip of the measuring part is flat in this example (FIG. 2C and does not protrude significantly above the ocular contact surface. Other variations include raising the tip of the measuring device (FIGS. 2A-2B) is raised above the ocular surface. This allows it to keep the eyelids from sliding over the top and bottom of the measuring component. This may help reduce intraocular infections and accidental contamination during injections.
“In other variations, a flange is used to contact the ocular surface (e.g. FIGS. 3A1-3A3, FIGS. 3B1-3B3, FIG. FIG. 4B1-4B2). 4B1-4B2). The pressure force per unit area at the interface may be reduced, which could reduce the risk of conjunctival injury by the device tip pressing against the eye wall. It is important to avoid conjunctival injury because the conjunctiva has delicate, non-keratinizing epithelium that contains multiple sensory nerve endings.
“In some cases, the flange may be curved so that the eye lid can travel over the top and along the ocular surface. However, it prevents the lid from touching the sterile ocular touch surface of the device tip. You may also find FIGS. 4A and 4B1-4B2 that the ocular contact surface can be a ring-shaped Flange. 4A, 4B1-4B2. This flange could also be used to prevent the eyelid from coming into contact with the sterile ocular contact surface at the device tip.
“More precisely, as shown at FIG. 3), the edge of the flange could be thin (FIG. 3A1) allows the eyelid to slide over the flange and contact the shaft of device tip. Alternately, the flange can be thicker (FIG. 3B1) to prevent the eyelid from sliding across it and keep it from coming into contact with the shaft. This will prevent inadvertent contamination. If the device tip’s flange is thick at the ocular contact, the edges of its edges may be rounded to protect the delicate, non-keratinizing epithelium that is rich in nerve endings or pain receptors. Alternate versions of the device tip may have a flat ocular contact interface (FIGS). 3A1 to 3B1, convex (FIGS), 3A2 and3B2, or concave. 3A3 and 3B3 are used to decrease the risk of injury to the ocular surface tissues, such as the conjunctiva. They also provide a way to apply a force on the eyewall and increase intraocular pressure to facilitate needle penetration. FIGS. FIGS.
“In further variations, the contact surface of the eye may be convex, concave or concave (e.g. FIGS. 5, 7). FIGS. FIGS. 5A1-5A2 show a device tip with a flat ocular contact area. Alternately, the device tip can have a protruding ocular contact surface or convex one (FIGS). 5B1-5B2, which can improve contact between the inner opening of the device tips and the ocular surface. This may reduce the risk of eye wall indentation when the device tip is pressed against a wall. Another variation is to have the device tip’s ocular contact surface indented or concave. This reduces the chance of injury to the conjunctiva and other ocular tissue. These configurations of the device tip’s ocular contact surface may decrease the risk of accidental damage to the ocular surface tissues such as the conjunctiva. They also provide a way to apply pressure to the eye wall and increase the intraocular pressure to facilitate needle penetration through it.
“More precisely, as shown at FIG. 7), the ocular contact surface can be perpendicular to its long axis (FIGS. 7A1-7A2 or flat and slanted relative the long-axis device (7B1-7B2), or convex and perpendicular the long-axis device (FIG. 7C1 or is convex, slanted relative the long axis (FIG. 7C2 or is round (FIG. 7D), or is oval. (FIG. 7E). One variation of the ocular interface can be rounded or oval (e.g. similar to 7E). The tip of a Qtip. The thickness of the contact surface can be between 0.01mm and 10mm, from about0.05mm to around 5mm, or from about 1 mm up to 2 mm.
One or more features, such as slip-reducing features, may be included in the ocular contact surfaces to help stabilize them on the eye surface. This helps prevent slippage. One variation of the Ocular Contact Surface may include one or more traction elements. These features could be bumps, ridges, raised details, etc. that increase the surface traction of the contact surface on the eye without being abrasive. This ocular contact surface can provide a medium-, high-, or strong-traction interface that stabilizes the device tip on the eye’s surface and prevents it from moving during intraocular drugs delivery. Another variation of the ocular surface is one that includes an adhesive interface, such as a suction mechanism. Variation in the material used to make an ocular contact surface can help to prevent slippage.
The materials used to create the ocular contact surfaces may help prevent irritation, scratching, and abrasion of the eye surface. Exemplary non-abrasive materials that may be employed include without limitation, nylon fiber, cotton fiber, hydrogels, spongiform materials, Styrofoam materials, other foam-like materials, silicone, plastics, PMMA, polypropylene, polyethylene, fluorinated ethylene propylene (FEP), and polytetrafluoroethylene (PTFE). When making contact with the eye, thermoplastic elastomers (e.g. silicone) may be useful. These materials can be either semi-hard or hard and can be used to prevent conjunctival abrasion or subconjunctival bleeding during transcleral needle deployment or any other accidental trauma to the ocular surfaces (FIG. 6). The durometer of an ocular contact surface material may range from 30 A to 60 A. These materials may also be used in contact lens manufacturing.”
“In certain variations, the edges on the ocular contact surfaces are also rounded to protect the tissues beneath the conjunctiva. This is because the conjunctiva is covered with delicate epithelium rich nerve endings and pain receptors. FIG. 6 The ocular contact surface could have a circumference that corresponds to the device tip’s circumference (FIGS. 6A1-6A2). Other variations may see the ocular contact surface protruding beyond the circumference the shaft of a device tip. This creates a flange (FIGS. 6B1-6B2). 6B1-6B2.
The ocular contact surface can also be flexible or deformable and conforms to the eye’s surface when it is placed against the eye during intraocular drug delivery. The eye’s surface that is in direct contact with said interface surface includes, but not limited to: the area of the eye covering the parsplana region, which is defined as the area around the limbus and the corneoscleral limbal. This area covers the area from about 2 to 7 mm past and around the limbus. An interface surface that conforms with the curvature on the eye’s surface may allow for the creation of an optimal contact interface between device and eye. This may help to ensure the safety of injection procedures and sterility in intraocular drug delivery. Ocular interface materials are materials that can conform to the eye’s surface (which is usually deformable or flexible) and in particular to the curvature at the pars plana, which is located about 2-5mm posterior to intravitreal drug application. Materials that are not abrasive to corneal epithelium and non-keratinizing conjunctival may be used. The materials and their configurations include foam, braid, knits, weave, fiber bundle, etc. These materials may be able to form medium- or high-traction surfaces (e.g. hydro gels or cotton), which enable the immobilization of eye globes during injection.
“In some cases, the material comprising the ocular contacts surface may change its properties when it comes into contact with fluid. This could include a reduction in its traction coefficient, such as in cotton fiber. This can reduce the risk of conjunctival damage from contact between the ocular surface and the eye surface. Other variations of the ocular contact surfaces do not experience any changes in their physical or chemical properties when they are exposed to fluids that cover the eye surface, such as tears.
“The ocular contacts surfaces may help to prevent conjunctival or episcleral bleeding when intraocular needle injection is performed. A device with a ring-shaped interface can be used to press against the eye wall. This pressure will then apply pressure to the episcleral and conjunctival vessels, reducing blood flow. The risk of subconjunctival bleeding may be decreased due to the reduced blood flow through these vessels. After intraocular drug application is completed, the needle can be withdrawn. However, the ring-shaped tip of the needle may still be pressed against the wall of the eye. This applies continuous pressure to the episcleral and conjunctival vessels, further reducing or minimising the risk of bleeding.
“In some variants, the device includes an ocular contact area that acts as a drug reservoir. The ocular contact surface can be coated with a drug or incorporated into it. The drug can then be diffused, leaked, or absorbed onto the eye’s surface via the ocular surface. Hydro gels and their derivatives are excellent materials for including drugs.
“Intraocular Pressure Control Mechanisms, Ocular Wall Tension Control Methods”
Controlling intraocular pressure (IOP), during drug delivery procedures, such as intravitreal injection or intraocular injection, can be helpful. Limiting intraocular pressure (or conduit) before dispensing the dispensing member may help to reduce scleral flexibility. This may in turn decrease the unpleasant sensation on the eye’s surface during injections and/or prevent backlash. Backlash is a term that refers to the inability of the conduit to penetrate the eye wall. Backlash is a term that refers to the inability to smooth penetrate the eye wall. This is usually due to scleral flexibility and elasticity. The devices described here may contain one or more IOP control mechanism, also known as ocular tension control mechanisms. Because intraocular pressure is a factor that determines ocular tension, it is also a factor that affects ocular wall strain. Wall tension can also be affected by scleral thickness or rigidity. These factors may vary depending on patient age, gender, and individual variations.
The IOP mechanisms can control IOP during placement and positioning the device tip at the target area on the ocular surface and/or intraocular and intravitreal positioning the dispensing member (conduit), during intraocular and intravitreal injections of a drug. The IOP mechanisms can control IOP before and during intraocular or intravitreal positioning a dispensing device member used for trans-scleral, trans-corneal penetration. IOP will decrease once the dispensing members have penetrated the ocular surface. The dispensing member may penetrate the ocular surface and cause a decrease in IOP.
“Some variations of the IOP control mechanisms enable the devices to generate an IOP of between 15 and 120mm Hg during placement and positioning the device tip at a target area on the ocular surface and/or intraocular positioning. Other variations of the IOP control mechanism allow the devices to generate an IOP of between 20 and 90mm Hg during placement and positioning the device tip at a target spot on the ocular surface and/or intraocular positioning. The IOP control mechanisms can be used to enable the devices to generate an IOP of between 25-60 mm Hg when the device tip is placed at a target spot on the ocular surface and/or intraocular positioning.
The IOP control mechanisms can also be used to keep the IOP between 10 – 120 mm Hg or between 15 – 90 mm Hg or between 20 -60 mmHg for any length of time during intraocular injections. The device may slow down or stop the drug injection rate if the intraocular pressure is higher than a predetermined value. For example, 120 mm Hg or 60 mmHg or 40 mmHg. The IOP control mechanism can be used to detect an IOP level, such as 90 mmHg or 60 mmHg or 40 mmHg during intraocular drug administration.
The IOP control mechanism can include a spring or a mechanical or electrical control mechanism. The IOP control mechanism is designed to balance fluid injection resistance pressure and frictional forces in the injection plunger. This is the force required to push fluid through a needle into pressurized eye fluids. The IOP control mechanisms can be connected to the device housing and actuation system in a way that allows for automatic adjustment of force of dispensing member deployment or advancement. The IOP control mechanism can be programmed to adjust the force of dispensing members and intraocular pressure levels. The IOP control mechanisms can be used to generate a higher IOP than the resting IOP before dispensing member deployment. This is to decrease scleral elasticity and reduce the risk of device backlash and facilitate dispensing members’ scleral penetration.
“In one variant, the IOP control valve is a pressure relief mechanism that bypasses an injection stream when a maximum pressure has been reached. Another variation of the IOP control mechanism is a pressure accumulation that dampens IOP within a defined range. The IOP control mechanism can include a pressure sensor in some variations. Another variation of the IOP control mechanism is a sliding cap or shield. This covers the dispensing unit prior to deployment. However, it may slide along the housing’s surface to expose, deploy or advance the dispensing members, e.g. after reaching a predetermined IOP level. The cap can be adjusted manually, such as with a dial, or it may be automatically adjustable, either step-wise or incrementally. FIG. FIG. 40 shows an example of integrated injection device 500. It includes a cap (502), stop (504), trigger (506), spring (508), plunger (508), seal (512), drug reservoir (514), needle (516) and a syringe (518) among others. When cap (502 is placed on the ocular surface with pressure applied, the cap (502) retracts proximally in the direction of the Arrow to stop (504), and the syringe (518), and needle (516), are advanced. To inject drug from the drug reservoir (514), through needle (516), trigger (506), e.g. a lever, can be depressed. Cap (502) is then placed over the needle (516).
A locking mechanism can also be used to stop the cap, cover, or ocular contact surface from sliding or prevent the dispensing device’s deployment until a predetermined IOP has been reached. If a predetermined IOP has not been reached, the locking mechanism can be used to stop sliding of the cover, cap, or ocular surface. The locking mechanisms on the devices discussed here, which include a sliding cover, cap, or other type of cover, can be released manually, or automatically, when the IOP reaches a preset level. For example, 20 mm Hg to 80 mmHg. These locking mechanisms include, without limitation, high-traction surfaces, locking pins and interlocking raisedridges. Any other locking mechanism that prevents a device’s tip, e.g. the cover or cap, from sliding out of reach of the needle, may also be used.
“In further variations, IOP control mechanisms include a high-traction surface, or raised ridges, on the cap, cover or shield, or ocular touch surface, over the dispensing device member. These features can be found on the inner surface the cap, cover or shield or ocular touch surface. They are designed so that when the dispensing member is moved in the proximal direction, any corresponding structures (e.g. crimps or dimples, protrusions or other raised ridges on the device housing) will mate with the raised ridges to provide resistance to the cap, cover or shield against the eye wall (thereby increasing the ocular wall tension or IOP). As described below, the IOP control mechanism includes a resistance component. As mentioned above, the cap or cover, shield or ocular contact surface can be designed so that sliding can be manually or automatically adjusted, either step-wise or incrementally. Any number of raised ridges may be used. They can be any size, shape and geometries. The raised ridges can be placed in the cover, cap, or ocular contact surface. Sometimes, raised ridges may be configured with sloped surfaces. The distal surface might be more steep than the proximal. This design allows for incremental sliding and incremental increases in IOP. The cap, cover or shield may be slid proximally. However, the decreased slope of proximal’s ridge surface may allow for sliding the cap, cover or shield back over the dispensing device.
When the shield is pushed onto the eye wall, the IOP control mechanisms may slip and expose the needle. The intraocular pressure may be between 10 mm and 150 mmHg, about 12 mm and about 120 mmHg, about 15 and 60 mmHg, or about 15 and 40 mmHg depending on the force exerted.
“Resistance Component”
“The injection of pressure on the surface of the eyes may be achieved by adding a resistance component (e.g., a dynamic resist component) to the injection device. The injection device may allow the dynamic resistance component to be detached from it. The housing may have a dynamic resistance component that includes a sliding element or a partially rotatable element (e.g. rotate 360 degrees) and a fully (or partially) rotatable element (e.g. rotate less than 360 degrees). The device’s dynamic resistance component can be designed so it can be rotated around the long axis using one finger (e.g. the middle finger), while being held with the thumb or index finger of the other hand. The slidable element may include a dynamic sleeve that adjusts the pressure on the eye surface. Certain variations of the ocular-wall tension control mechanism can also function as dynamic resistance elements, as previously mentioned. To initiate the movement of the slidable element against the resistance generated by the sliding elements, a force between 5 gm and about 00 gm (or about 10 gm-about 30 gm) may be required. It may take from 20 gm to 25 gm for the slidable elements to move in some variations. Other variations may require from 3 gm to 30 gm force to move the slidable resistance element.
The dynamic resistance component can also be used as a dynamic sleeves. The dynamic sleeve can be used to increase intraocular pressure or tension before needle injections, similar to the slidable caps. The dynamic sleeve can be manually adjusted to adjust the pressure on the surface of the eyes and thus the tension in the eyewall. The ability to adjust the pressure manually may enable the injector to improve control over the injection site location and angle. It also allows the user to position the device more accurately on the ocular surface before needle deployment. The dynamic sleeve allows the user to position the device tip precisely on the eye surface. They can also press the tip against the wall to increase intraocular pressure and wall tension. You can use the dynamic sleeve to increase intraocular pressure, as described above. The terms “dynamic sleeve” and “sleeve” are interchangeable. ?sleeve,? ?slidable sleeve,? ?dynamic sleeves resistance control mechanism? ?sleeve resistance control mechanism,? They are interchangeable throughout. Some variations of the dynamic sleeve are removable or easily detached from the drug conduit. This leaves the drug conduit entirely exposed. Other variations of the dynamic sleeve are fixed to the drug conduit and cover at least part of the conduit. The dynamic sleeve can be either rigid or non-deformable in further variations. A dynamic sleeve can be designed so that, when a pulling force (e.g. retraction away form the eye) is applied to the sleeve this movement may facilitate needle access and reduce the pressure force (down down to 0 Newton) (??N? Refers to the unit force,?Newton? To slide the sleeve back, the needle must be exposed by applying pressure to the eye wall. A dynamic sleeve can also be designed so that when a pushing force (e.g. advancement) is applied to the sleeve this movement may counteract and prevent needle exposure. This may allow the device tip or the device to apply more pressure to the eyewall prior to the initiation sleeve movement.
“Some versions of the dynamic sleeves provide a variable force that follows an U-shaped curve as described in Example 1 or FIG. 46. This is where the most resistance occurs. There is less resistance between the end and start of dynamic sleeves movement along the housing. This means that the needle will have a high resistance phase upon placement on the eyewall. Then, the resistance to sleeve movement is decreased during needle advancement into eye cavity. The needle will be fully deployed when the dynamic sleeve is at the end its travel path. This will result in increased resistance. The sleeve can come to a gradual, smooth stop instead of abruptly stopping at the end point. This reduces the chance of damaging the inert eye walls and minimizing the risk of discomforting or injuring the eye. An example dynamic sleeve might be tapered at both the distal and proximal ends. FIG. 42. The integrated injection device (42), includes a housing (44), resistance band (46) which is either entirely or partially around the housing and a dynamic sleeves (48), that can slide forward and backwards upon the housing (44) The resistance band that surrounds the housing is sometimes called a resistance strip. The tapered ends of the dynamic sleeves (48) have a proximal (50) as well as a distal (not shown). The tapered ends can provide greater traction along the device housing (44), which is where needle deployment begins and ends. The taper at its proximal (50) is more effective in providing traction and resistance when the dynamic sleeve moves towards the resistance band (46). You can adjust the amount resistance you desire by changing the thickness of the resistance bands (46) The resistance band’s thickness can be adjusted to adjust the amount of resistance desired. It may vary in thickness from 0.01 mm up to 5 mm or from 0.1 mm down to 1 mm. The resistance band’s thickness can be as low as 0.05 mm. It could also range from 0.01 mm to about 5 mm. The width of resistance bands can also vary. It may be as wide as 1.0 mm or 1.5 mm. About 2.5 mm. about 3.0mm. about 3.5mm. about 4.0mm. about 4.5mm. or 5.0mm. The wider middle segment (52) will result in lower-traction and resistance movement. This is followed by higher resistance and traction at the end needle deployment due to the taper at distal end. The dynamic sleeve gradually tapers at the distal ends, producing more traction against the housing until it eventually stops. In some cases, the tapered ends may not be both the distal and proximal ends of the dynamic sleeves.
Components such as circular raised bands and ridges at the tip of the device may provide variable traction. These components can provide counter-traction when they are compared to another circular raised band, ridge or ridge on a movable dynamic sleeves (inner bands and ridges). The outer and inner bands, or ridges, that come into contact with one another before dynamic sleeves move generate high traction. The raised band on one side of the device housing may move past the raised band inside the dynamic sleeves. This can cause a rapid decrease of resistance to dynamic sleeves movement, and therefore less pressure on the eyewall by the device tip. The resistance decrease will be determined by the shape of the interlocking bands and ridges. The profile of resistance decrease can be sine-shaped, for example.
“The resistance component can also be coaxially mounted with the housing and have a lumen and an interior surface that form a step or platform around at least some of it. Some variations of the slidable barrier shield have the platform or step circumnavigating the entire lumen. To provide greater friction (resistance), the shield slides along its housing’s luminal diameter, the platform or step generally reduces the shield’s lumen. The internal diameter of the slidable cover may be smaller in the distal than the proximal. The platform or raised step’s width can range from 0.1 to 5 mm or 0.5 to 2 mm. A raised platform or step may have at least one sloped or rounded edge. This could be either the distal or proximal edge. A raised platform or step may also have an edge that is gradually sloped in order to increase the lumen diameter and reduce friction when the shield slides to expose the needle. The edge can be slopped so that the lumen is larger in the proximal than the distal part of the shield.
Another variation is that the force generated by the dynamic sleeves may decrease from its highest point prior to needle deployment (when it completely covers the needle), down to its lowest point, when the dynamic sleeves begins to move and expose the needle tip. This force stays low until needle deployment and the end of dynamic sleeves travel. This curve of resistance may be a sine-shaped one.
Slideable advancement of a dynamic sleeve can generate resistance forces against its movement that range from 0 N up to about 2N. In other instances, it may generate a force of about 0.1 N to approximately 1 N. The force required to move the sleeves may range from 3 gm to 30 gm.
The resistance component can be attached to an injector attachment, or to an injector assembly that is easily removed from any suitable syringe. This includes syringes with luer lock or luer slip types. The injector attachment’s resistance component may interface with either the external or internal surfaces of a sliding sleeve. Some injector attachments include a disc-shaped or ring-shaped component. This is usually raised above the surface and surrounds at least part of the injector attachment’s exterior. The ring can be used as a handle or grip to manipulate the injector attachment. FIGS. FIGS.
“In certain cases, the resistance component may contain a number of appendages attached or formed as part the needle hub. The device could be designed to have an injector attachment, which can be used to replace the normal loading needle. An injector attachment could include a sterile injection tool (e.g. a 30-33 gauge needle) or a resistance component (e.g. a dynamic sleeve). This modular design has the advantage that drug can be loaded as a regular syringe, so side loading is not necessary. A universal female connector may be included in such a modular assembly. It might include a flange at the attachment’s proximal end. The female connector can allow the injector attachment (i.e. attach and detach) to be removably interfaced with a male-luer-tip drug storage reservoir. A syringe may have a drug reservoir that has a luer fitting for the luer Jock, luer slip configuration or any derivative of the tip. Modular design allows for loading a drug reservoir into any of these devices with a drug vial or container. To transfer the drug from the vial into the reservoir, a loading needle is first needed. You can then remove the loading needle or switch it for an injector attachment.
“For example, see FIG. 53 shows an example injector attachment (1500). The injector attachment (1500), includes a needle hub (11502) that allows for the removal of the attachment (1500). The needle hub (1502) can be configured with multiple projections (1504) that extend distally beyond the needle hub. The figure shows four projections, but you can use any number of projections to the needle hub. You can use six projections or two projections. Any suitable material can be used to make the projections. The projections can be made from any suitable material. One variation of the projections is made from polypropylene. You can also have the projections radially placed around the hub’s periphery in any way you like. The projections can be placed in any way you like, including equally spaced or unevenly spaced. They may also be symmetrically or asymmetrically spaced around the hub’s periphery. The slidable shield (1506) may cover the projections (1504) and needle hub (1502), or may be operatively connected to an ocular contact surface with a measuring component (1508). The projections provide friction (resistance), with the internal surface. You may need to overcome the desired resistive force to advance the resistance (e.g. the slidable Shield) by varying between about 0.01 grams and 100 grams or between about 5.0 grams and 30 grams. FIG. 59. Other friction profiles may also be considered, which could require constant force, increasing force, or a combination of both. You can adjust or optimize the amount of friction by changing the material comprising the contact surfaces, such as by increasing the contact surface or narrowing the slidable-shield lumen’s internal diameter. There may be an interference fit between the projections and the slidable screen in some cases. The interference fit can vary from 0.05 mm to about 1.0mm (about 0.04inches) or from 0.08mm to 0.0.003inches to 0.76mm (about 0.03inches). An interference fit of 0.13mm (about 0.005 in) between the inner diameter (inside diameter), of the slidable cover and the outer diameter (outer diameter) of the needle hub assembly could result in a range of resistance force of approximately 3 to 30 grams. A 2% to 5% interference is sufficient to provide adequate resistance. The interference will be greater the more flexible (i.e. less rigid) the projections. To facilitate smooth sliding, either or both of the contact surfaces can be lubricated or coated. One variation is to place a smooth mobility element (e.g., silicone or thermoplastic-elastomeric washer) inside the shield to create smooth sliding with the drug conduit, the internal surface lumen of shield, or to apply a coating (e.g. a fluoropolymer coat or a lubricant to at least one friction/traction area).
However, shield (1506) movement may not be blocked by all of the projections (1504) You can use any number of projections (1504) to provide resistance. One or two projections from four could be used to provide resistance. Non-resistance projections may be used to provide sliding limits for shields, such as forward and rearward. They may also stop the shield rotating relative to its axis. Attached to the hub (1502) is the needle (1514). It extends distally from there. The force curves, decreases of resistance and amount of force generated by the projections and slidable shield could be identical or similar to those described for dynamic sleeves.
The internal surface of the slidable sleeves may have one or more longitudinal grooves. The grooves can extend through the wall of the sleeves, whether it is full thickness or partial. The grooves prevent the sleeve spinning or rotating around its long axis by allowing the projections of the hub (or needle assembly) to travel within the grooves. The grooves that prevent the sleeve from rotating may be used when the circumference of the tip is 360 degrees. This means that the measuring component does not need to rotate in order to point the measuring part towards the limbus.
The needle can be attached to a hub with multiple projections. A shield, such as the one in FIGS. You can slide the shield 54B or 54C over the needle hub until it snaps into place. The shield is secured to the needle hub using no adhesives. To prevent the shield from moving forward and backward, a safety clip may be attached to your needle hub. Any suitable material can be used to make the needle hub. The needle hub may be made of polypropylene in some cases. Other variations of the needle hub are made from polypropylene. You can also make the slidable shield from any material. The slidable shield can be made of a polycarbonate or polished polycarbonate.
Some safety clips create resistance that hinders shield movement relative to drug conduit. The clip may lock the shield in a specific position or multiple positions (pre-deployment resting place, post-injection ending position, or both) and prevent it from moving relative to the drug conduit. One variation of the safety clip is that it does not rotate relative the device’s long axis. Another example is that the safety clip can be rotated relative to the device’s long axis.
FIGS. 54A-54C. 54A-54C. The injection device (1600), is shown in these figures as consisting of a syringe (1604) with a proximal and distal ends (1606). The distal end (1606) can be removably connected to an injector attachment (1608). This variation is illustrated in FIGS. 54B and 54C: Injector attachment (1608) includes an injector hub (1610) with a proximal and distal ends (1611), 1612 and 4 projections (1614). Any number of projections can be used, as stated previously. The projections (1614), can be configured, shaped and so on. At their distal ends, a tab (1616) is placed. The distal ends can be made with hooks, flaps or tabs instead of tabs. The injector attachment (1608), also includes a sliding shield (1618), with a proximal and distal ends (1620) and slots (1624) that are provided through or partially through the shield (1618). Slots can be any size, shape or geometry and are designed to interact with the slots in a complementary manner. The projections (1614), generally have a slight interference fit to the inside of the slidable Shield (1618). A distal end (1622), of the shield (1618) can have an ocular contact surface with a measuring component (1626). The projections (1614), which slide along the shield’s inside surface (1618), provide resistance to shield (1618). The shield (1618) provides resistance until the projections (1614), reach the slots (1624). The tabs (1616), at the distal ends (1614), expand (e.g. radially expand), into the slots (1624), decreasing resistance to movement of shield (1618). You can adjust the resistance by changing the thickness of tabs and the interference between the projections and the shield’s inner surface. To prevent axial movement of shield (1618) along outer surface (1610) of needle hub (1610), a clip (1607), may be attached to the hub (1610). The clip (1607), which can be removed, can prevent the shield (1618 from moving axially). Clips may be used to prevent the resistance component (e.g. the slidable shield) from moving longitudinally along the device’s axis. Any configuration of the clip is possible that will prevent axial movement of shields when they are coupled to the needle hub. However, it can allow for axial movement when the needle bub is removed. Some variations of the clip can be secured to the housing of the device or the needle hub assembly, so it doesn’t rotate around the housing (e.g. about the longitudinal axis). Other variations may allow the clip to rotate around the housing. As described further below, in some cases, a locking mechanism such as a clip that controls mobility of the dynamic shield/sleeve may be non-removable attached to the housing, shield, needle hub/assembly or drug reservoir or any other part of the device. The locking mechanism can be released by pressing the rear lever. This will release the sliding shield and make it mobile.
Clips that attach to the injector device’s portion or attachment can also be used. Clips can be made in any configuration to prevent the resistance component from moving. You can attach some clips to the housing of your device, while others may be attached to a section of the needle assembly. FIG. The clip could be a lever (6002) attached to the needle assembly (6044) of the device (6000). Lever 6002 has two ends. One end contains a release tab (6006) while the other end has a locking shoulder (608). FIG. 63B) The locking shoulder (6008) touches a portion the resistance mechanism (shown as 6010) to stop the movement of the 6010 slidable sleeves (6010) The release tab (6006) should be depressed in the direction shown in FIGS. 63C-63D: When the release tab (6006) is depressed, the lever (6002) pivots at the point of fixation to needle assembly (6004) so the end with locking shoulder (6008) can be lifted, e.g. in the direction indicated by arrow B. Lifting the locking shoulder (6088) will remove contact between the locking shoulder (6068) and the slidable sleeves (6010) and the slidable shoulder (6010) will allow the slidable shoulder (6010) to slide proximally. The slidable sleeves (6010) can be again locked against movement after injection is completed. Press the locking shoulder (6008) until it touches the slidable sleeves (6010)
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