Eye device and drug delivery system and housing

Abstract

An ocular device for placement under an eyelid includes a plate having a posterior surface with at least one protrusion having a convex contact surface that contacts a sclera of an eye and provides an offset space. The plate can be connected to an elongated support member. The ocular device can deliver a substance to an eye of a user, the substance including, for example, a pharmaceutically active agent. A housing for holding and dispensing an ocular device includes a compartment configured to hold a fluid, a stabilizer, and a cover. The cover is connected to the compartment and rotatable between a position covering the compartment and a position in which the compartment is uncovered. The cover can have a port for adding fluid to the compartment, and a receiver of an ocular device can extend from the cover.

Description

[0001] Related applications

[0002] This application claims the benefit of U.S. Provisional Application No. 62 / 925,695, filed October 24, 2019. The entire teachings of the above application are incorporated herein by reference. Background Technology

[0003] Devices for delivering medication to the eye have a long history of use for a variety of purposes. An early example is a pair of glasses with a drug chamber, which would be worn on the eye to administer and deliver medication to the eye over a set period of time. This example demonstrates a clinical device for treating the physiological functions of the eye through direct contact.

[0004] Over time, the field has evolved to include devices and / or substances containing therapeutic agents designed for independent placement within the anatomical space of the eye. Examples include structures and drug delivery systems designed to be positioned and held within the anatomical space of the eye in a manner that can provide a uniform drug delivery rate to the eye, and geometries designed for this purpose. This historical migration of direct application to clinical treatment has resulted in a variety of therapeutic modalities.

[0005] Eye-connecting devices have evolved over time, encompassing smaller and more complex devices. Many of these devices require placement within the eye space in a specific orientation. For example, contact lenses are placed on the eyeball with one surface against the eye and the other not. Typically, the user identifies the surface of the contact lens to be applied to the eye. For eye-connecting devices designed for placement in a specific orientation, it is advantageous to simply and clearly indicate the preferred orientation to the user. Current practices for eye-connecting devices such as contact lenses involve identifying the left and right eye devices to the user.

[0006] Users may not be able to determine the correct orientation of eye-connecting devices, which are smaller and more complex than contact lenses. Eye-connecting devices that are not placed on the cornea present challenges for proper placement and orientation. Without proper placement and orientation, these devices may function improperly or suboptimally. Summary of the Invention

[0007] Eye-mounting devices can be placed inside the eye. Contact lenses are eye-mounting devices placed on the surface of the eyeball. Eye-mounting devices can be placed under the eyelid. The eyelid can be the upper or lower eyelid. People with dry eye syndrome may have a weakened ability to form a lacrimal meniscus and may have reduced tear volume, and tear production may decrease with age. A comfortable, adaptive hydrophilic (absorbent) eye-mounting device placed under the eyelid can be beneficial because, for example, it can collect tears, and thus increase the volume and residence time of tears. Eye-mounting devices may include features configured to retain tears, potentially enabling the retention of large amounts of tears, which is desirable in, for example, older individuals and users with dry eye syndrome who experience difficulty achieving adequate eye lubrication. Eye-mounting devices placed under the eyelid can be used, for example, to deliver therapeutic agents to the eye. Placing an eye-mounting device under the eyelid is advantageous because it can accommodate differences in eye anatomy and eye dynamics among different patients, including differences that may be caused by factors such as age, health, and genetic or ancestral factors.

[0008] An eye-receiving device placed under the eyelid includes a plate. The plate includes a posterior surface having at least one protrusion with a contact surface that contacts the sclera of the eye and provides offset space between the sclera and the posterior surface of the plate. Inserting the device into the eye further offsets the eyelid relative to the sclera.

[0009] The plate can be connected to an elongated support member made of a flexible material, the elongated support member having a first end and a second end. The plate may be connected near the first end of the elongated support member. The receiving device may also include a plate connected near the second end of the elongated support member.

[0010] A flexible connector can connect at least one plate to the elongated support member. The connection between the flexible connector and the elongated support member can be configured to be positioned adjacent to the corner of the eye when the eye-receiving device is under the eyelid. The contact surface can form a boundary around the offset space.

[0011] The at least one protrusion may be a complete ring. The at least one protrusion may be annular.

[0012] The rear surface of the plate may have at least three protrusions, each protrusion having a contact surface that contacts the sclera of the eye and provides offset space between the sclera and the rear surface of the plate. The contact surface of the at least one protrusion on the rear surface may be a convex contact surface.

[0013] Each plate includes a front surface on the opposite side of the plate relative to the rear surface. The front surface may have at least one protrusion with a contact surface that contacts the sclera of the eye and provides offset space between the sclera and the front surface of the plate. The contact surface of the at least one protrusion on the front surface may be a convex contact surface.

[0014] The periphery of at least one plate of the receiving device may be curved.

[0015] At least one plate of the receiving device may extend laterally from an elongated support member.

[0016] The length of the elongated support member of the eye-catching device can be between approximately 3 mm and approximately 24 mm. The length of the elongated support member of the eye-catching device can be between approximately 3 mm and approximately 8 mm. The length of the elongated support member of the eye-catching device can be between approximately 4 mm and approximately 10 mm. The length of the elongated support member can be between approximately 6 mm and approximately 16 mm.

[0017] The elongated support member, the plate connected to the first end near the elongated support member, and the plate connected to the second end near the elongated support member can be substantially coplanar, flexibly interconnected, and configured to suit irregular surfaces.

[0018] At least one plate may be connected to the elongated support member between the first end and the second end of the elongated support member of the receiving device, the at least one plate being substantially coplanar with the elongated support member.

[0019] The receiving device may include at least three plates.

[0020] Each plate of the connector can be connected to a slender support member via a flexible connector.

[0021] At least two plates of the eye-connecting device can be connected to the elongated support member via flexible, curved connectors, and at least two other plates of the eye-connecting device can be connected to the elongated support member via flexible, substantially straight connectors.

[0022] The thickness of at least one of the plates in the receiving device can decrease from front to back with distance from the central region of the receiving device.

[0023] The plate of the connector can be connected to the same side of the slender support member.

[0024] The connection device may include a curved, elongated support member. The connection device may include an elongated support member having a smoothly curved outer surface.

[0025] The receiving device may include at least one generally circular plate.

[0026] The receiving device may include at least one plate having a rear surface, wherein the widest portion of the rear surface of the at least one plate is about 2 mm to about 7 mm.

[0027] The receiving device may have a generally circular plate. The generally circular plate may have a diameter ranging from about 2 mm to about 7 mm.

[0028] The sight-catching device may have an elongated support member having an arched portion and an outer sloping portion, each outer sloping portion extending from the arched portion. The arched portion of the elongated support member may have a radius of curvature between approximately 0.0 mm and approximately 6.0 mm. The arched portion of the elongated support member may be a segmental arch located in the central region of the sight-catching device between the ends of the elongated support member.

[0029] An eye-contact device may have a substance to be delivered to the eye. The substance to be delivered to the eye may be in at least one plate of the eye-contact device. At least one plate of the eye-contact device may provide at least one recess for holding the substance to be delivered to the eye. The recess in the plate may be cylindrical. The substance to be delivered to the eye may be in the recess in the plate. The plate may have an opening leading to the recess, wherein the recess is configured to receive the substance to be delivered to the eye through the opening.

[0030] An insert containing the substance to be delivered to the eye can be placed in a recess in the plate of the eye-contact device.

[0031] The connector may have a retaining element that holds the insert in the recess. For example, the retaining element may be a sealing diaphragm coupled to the connector, coupled to the insert, or coupled to both the connector and the insert. The sealing diaphragm used as the retaining element may include an aperture. The lip at the opening of the recess may serve as the retaining element. The opening to the recess may be generally polygonal in shape. The opening to the recess may be generally hexagonal in shape.

[0032] An orifice may be present in the plate of the eye-contact device, which is configured to dispense the substance from an insert in the plate through the orifice into the eye. The orifice may be different from the opening and provides a bidirectional drug delivery system.

[0033] At least a portion of the receiving device may be formed of a polymer material.

[0034] An eye-accessing device placed under the eyelid includes an elongated support member made of a flexible material and at least one plate connected to the elongated support member. The plate has a posterior surface with at least one protrusion having a contact surface that contacts the sclera of the eye and provides offset space between the sclera and the posterior surface of the plate. The contact surface may be convex. The elongated support member and the plate may be substantially coplanar. The at least one plate may be connected to the elongated support member near an end of the elongated support member. The eye-accessing device may have at least two plates connected to the elongated support member near an end of the elongated support member, the elongated support member and the plates being substantially coplanar. The eye-accessing device may include at least three plates connected to the elongated support member.

[0035] An eye-contact device placed under the eyelid to deliver a substance to the eye includes an elongated support member and plates connected near each end of the elongated support member, the plates being substantially coplanar with the elongated support member. Each plate includes a posterior surface having at least one protrusion with a contact surface that contacts the sclera of the eye and provides offset space between the sclera and the posterior surface of the plate. The contact surface may be convex. The eye-contact device may further include a pharmaceutically active agent. The pharmaceutically active agent may be disposed within at least one plate.

[0036] An eye-contact device placed under the eyelid can deliver substances such as pharmaceutical active agents to the eye by forming at least a portion of the eye-contact device with a pharmaceutical active agent blended with other substances.

[0037] The receiving device may include at least one plate having a recess capable of receiving a pharmaceutically active agent. The pharmaceutically active agent may reside in the recess of the plate of the receiving device. A removable insert containing the pharmaceutically active agent may reside in at least one of the recesses. The plate may also include a retaining element for holding the insert within the recess.

[0038] An eye-contact device placed under the eyelid includes: a scleral contact surface having at least three points configured to contact the sclera of the eye; and a distal surface configured to retain the sclera distal to the eye via the at least three contact points, the distal surface and the at least three contact points providing offset space configured to retain tear fluid. The eye-contact device may further include a pharmacologically active agent for delivery to the eye. The eye-contact device can be placed under the eyelid, and the pharmacologically active agent can be delivered to the eye via tear fluid.

[0039] An eye-contact device placed under the eyelid may have a contact surface for contacting the sclera that is approximately 20% smaller than the surface area of ​​the distal surface. The eye-contact device may be flexible and adapted to the scleral contact surface.

[0040] A method for delivering a pharmaceutically active agent to an eye includes the steps of: providing an eye-connecting device having: an elongated support member; plates connected near each end of the elongated support member, the plates being substantially coplanar with the elongated support member, at least one plate having a posterior surface, the posterior surface having at least one protrusion, the at least one protrusion having a contact surface that contacts the sclera of the eye and provides offset space between the sclera and the posterior surface of the plates; adding a pharmaceutically active agent to at least one of the plates; and placing the eye-connecting device under the eyelid. The contact surface may be convex. Adding the pharmaceutically active agent to at least one of the plates of the eye-connecting device may include: disposing the pharmaceutically active agent in at least one recess in at least one of the plates. Disposing the pharmaceutically active agent in the at least one recess may include: inserting an insert containing the pharmaceutically active agent into the at least one recess.

[0041] The eye-connecting device can be placed under the eyelid with the rear surface of at least one plate facing the sclera of the eye. The eye-connecting device can be placed under the eyelid with the front surface of at least one plate facing the sclera of the eye. The eye-connecting device can be placed under the eyelid with the elongated support member facing the dome. The eye-connecting device can be placed under the eyelid with at least one plate facing the dome.

[0042] An insert for use with a contact device or method may comprise, substantially comprise, or comprise of a pharmaceutically acceptable carrier containing a pharmaceutically active agent and a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier may comprise a water-soluble polymer. The pharmaceutically acceptable carrier may comprise a water-insoluble polymer. The pharmaceutically acceptable carrier may form a matrix, and the pharmaceutically active agent may be dispersed in the matrix.

[0043] A composition comprises: one or more pharmaceutical active agents; about 20% to about 80% by weight of a water-insoluble polymer; and about 20% to about 80% by weight of a water-soluble polymer. The composition may include about 25% to about 70% by weight of the water-insoluble polymer. The composition may include about 40% to about 75% by weight of the water-soluble polymer. The water-insoluble polymer of the composition may be ethylene vinyl acetate (EVA). The weight percentage of vinyl acetate in EVA may be 25% or greater. The water-soluble polymer of the composition may be polyethylene oxide (PEO). The molecular weight of PEO may be about 100,000 to about 300,000. The water-insoluble polymer of the composition may have a melting temperature of about 99°C or lower. The water-soluble polymer of the composition may have a melting temperature of about 99°C or lower. The composition may contain about 0.5% to about 50% by weight of the pharmaceutical active agent. Each of the one or more pharmaceutical active agents may have a melting temperature above about 99°C and be water-soluble. The one or more pharmaceutical active agents may be in particulate form. The one or more pharmaceutical active agents may include ciprofloxacin, dexamethasone, olopatadine, pilocarpine, hyaluronic acid, or hydroxypropyl cellulose, or a pharmaceutically acceptable salt thereof.

[0044] The composition can be formulated for ocular application. The composition can be in the form of a semi-eraseable polymer matrix. The composition can be formulated to provide a controlled release of one or more pharmaceutically active agents.

[0045] A method for preparing the disclosed composition includes: hot-melt blending one or more pharmaceutical active agents, a water-insoluble polymer, and a water-soluble polymer to form a hot-melt blend; and cooling the hot-melt blend to produce the composition. Hot-melt blending can be performed at temperatures below about 99°C. Hot-melt blending can be performed at temperatures below the melting temperature of the one or more pharmaceutical active agents.

[0046] A housing for holding and dispensing a contact device includes: a compartment configured to hold fluid, the compartment having an open top; a stabilizer connected to the compartment; a cover connected to the compartment, the cover being rotatable between a position covering the open top of the compartment and a position where the compartment is uncovered, the cover having a port in fluid communication with the interior of the compartment when the cover covers the open top of the compartment; and a receiver extending from the cover and configured to receive and hold the contact device near the port, the receiver being within the compartment when the compartment is covered by the cover.

[0047] The receiver of the housing may form a channel that is open on at least one side of the receiver. The channel may be open on both sides of the receiver, and the channel may be configured to allow the receiving device to be dispensed from either side of the receiver, thereby maintaining the orientation of the dispensed receiving device. The channel may be shorter than the receiving device. The receiver may include a restraining element configured to hold the receiving device in a specific orientation. The restraining element may be a ridge.

[0048] When the cover is in the position covering the open top of the compartment, the cover can be removably secured to the compartment, and the cover can be configured to extend through the compartment when the cover is in the position covering the open top of the compartment.

[0049] The housing may include a latch for removably securing the cover to the position covering the open top of the compartment. The latch may be a latch post and a key.

[0050] The cover can be connected to the compartment via a hinge made of a flexible material.

[0051] The stabilizer can form a ring around the compartment.

[0052] The compartment, the stabilizer, the cover, and the receiver can be an integral construction.

[0053] The port can be configured to allow fluid to enter the compartment when the cover is in the position covering the open top of the compartment. The length of the port is sufficient to allow gas to escape from the compartment and allow fluid to enter the compartment.

[0054] The housing may include a removable peel strip that seals the port.

[0055] The shell can be made of a polypropylene material with high melt flow.

[0056] The housing may have a receiving device within the housing.

[0057] The housing may include features for orienting the receiving device. These features for orienting the device may be tactile or visual features.

[0058] The housing can be used to hold and dispense the receiving device, which includes the receiving devices disclosed herein.

[0059] The receiver of the housing may further include a restraining element. The restraining element may be a ridge.

[0060] A housing for holding and dispensing a contact device includes: a compartment configured to hold fluid, the compartment having an open top; a stabilizer connected to the compartment; a cover connected to the compartment, the cover being rotatable between a position covering the open top of the compartment and a position where the compartment is uncovered; and a receiver extending from the cover and configured to receive and hold the contact device, the receiver being within the compartment when the compartment is covered by the cover.

[0061] The housing may include a port. The port may be on the cover and in fluid communication with the interior of the compartment when the cover is in the position covering the open top of the compartment. A receiving device held by the receiver may be located near the port.

[0062] The port can be configured to allow liquid to enter the compartment and flow across the receiving device when the cover is in the position covering the open top of the compartment.

[0063] A kit may be provided comprising an eye contact device, a housing, and a substance for application to a user's eyes. The substance may be a medicine, a drug, a pharmaceutical product, or a combination thereof. The kit may include a solution for wetting the eye contact device.

[0064] A method for inserting an eye-receiving device held in a housing by a receiver into a user's eye, the eye-receiving device having a surface for contacting the sclera of the eye. The method includes the steps of: positioning the housing in a generally flat position in front of the user such that the surface of the eye-receiving device to contact the sclera is oriented toward the user; rotating a cover of an open top of a compartment covering the housing to remove the receiver from the compartment and expose the eye-receiving device held by the receiver; removing the eye-receiving device from the receiver while maintaining its orientation; and inserting the eye-receiving device into the user's eye, under the eyelid.

[0065] The method may further include: disinfecting the contact device sealed in the compartment while the cover is in the position covering the open top of the compartment.

[0066] The method may further include adding a substance to be applied to the user's eyes into the compartment. The substance may be added through the port.

[0067] Material can be added directly to the interior space of the compartment through the open top of the compartment.

[0068] The method may include: removing a stripping strip from the cover, and removing the stripping strip may unseal the port.

[0069] Before the cover rotates, the cover may be the open top covering the compartment, and the port may be in fluid communication with the interior space of the compartment.

[0070] Removing the receiver from the housing can be achieved by pulling a handle, allowing the protruding portion of the receiver to be grasped from the left or right side of the receiver with either the left or right hand. When removing the receiver, a pusher can be used to guide the protruding portion of the receiver toward the puller. Attached Figure Description

[0071] The above will become clear from the following more specific description of exemplary embodiments illustrated in the accompanying drawings, in which similar reference numerals are used to denote the same parts in different views throughout the drawings. The drawings are not necessarily to scale, but rather focus on illustrating the embodiments. The descriptions of the drawings, which identify "front," "rear," "top," and "bottom" views, provide a frame of reference and are not intended to limit the direction of use of the content appearing in the drawings.

[0072] Figure 1 It is an isometric view of a three-dimensional (3D) model of an eyeball with normal focus (the focus of an emmetropic eye), which identifies the sagittal (vertical) plane, the transverse (horizontal) plane and the optical axis as spatial references and shows the degrees of freedom.

[0073] Figure 2A It is an isometric view of a model of the eyeball, showing the surface and sagittal plane of an emmetropic eye.

[0074] Figure 2B This is a horizontal sectional view of the eyeball, illustrating the corresponding... Figure 2A The axial length and lateral width measurements of the normal eye.

[0075] Figure 2C , Figure 2D , Figure 2E and Figure 2F This is a sectional view of the eyeball, which shows the anatomical measurements of axial length and lateral width observed during clinical assessment, as further summarized in Table 1.

[0076] Figure 3A It is an isometric view of a representative eyeball and eyelid without specific parameters.

[0077] Figure 3B yes Figure 3A A side view of the eyeball and eyelids.

[0078] Figure 4AThis is a frontal view of the eyeball with eyelids representing people aged 20 to 30, as shown in Table 1. This view is shown as a sectional view in a vertical plane.

[0079] Figure 4B yes Figure 4A A cross-sectional view of the eyeball and eyelids, showing the average upper eyelid depth (“UFD”) and the average lower eyelid depth (“LFD”).

[0080] Figure 4C It is a frontal view of the eyeball and eyelids of a person who has palpebral fissure width (“PFW”), which is more likely to be observed in a particular population as a measure of the average canthal width of smaller eyes, and is shown as a sectional view in a vertical plane.

[0081] Figure 4D yes Figure 4C A cross-sectional view of the eyeball and eyelids, showing the minimum UFD and LFD.

[0082] Figure 4E It is a frontal view of the eyeball and eyelids of a person with PFW, which is more likely to be observed in a specific population as a measure of average canthal width of larger eyes, and is shown as a sectional view in a vertical plane.

[0083] Figure 4F yes Figure 4E A cross-sectional view of the eyeball and eyelids, showing the maximum UFD and LFD.

[0084] Figure 5A This is an isometric view of an example of a receiving device.

[0085] Figure 5B yes Figure 5A A bottom view of the receiving device.

[0086] Figure 5C yes Figure 5A Front view of the receiving device.

[0087] Figure 5D yes Figure 5A An isometric view of the receiving device, showing... Figure 5A The adaptability of the receiving device has multiple degrees of freedom.

[0088] Figure 6A This is an isometric view of an example of a slender support member used in a receiving device.

[0089] Figure 6B This is an isometric view of an example of a slender support member used in a receiving device.

[0090] Figure 6C yes Figure 6BAn isometric view of the slender support member, including a vertical axis, a horizontal axis, a torsional axis, and associated arrows indicating rotational degrees of freedom. These axes are provided for reference only and are not part of the device.

[0091] Figure 6D This is a front view of an elongated support member, in which a plate is connected to the elongated support member, and the view shows a flexible connector.

[0092] Figure 6E yes Figure 6D An isometric view of the apparatus, including a vertical axis, a horizontal axis, a torsional axis, and associated arrows indicating rotational degrees of freedom. These axes are provided for reference only and are not integral parts of the apparatus.

[0093] Figure 6F This is a front view of an elongated support member with a plate connected to it, showing a flexible connector.

[0094] Figure 6G yes Figure 6F An isometric view including a vertical axis, a horizontal axis, and a torsional axis, along with associated arrows indicating rotational degrees of freedom. These axes are provided for reference only and are not part of the device.

[0095] Figure 7A It is a frontal view of a portion of the eye, in which the lower eyelid is partially removed to expose the eye-receiving device placed and positioned inside the eye.

[0096] Figure 7B yes Figure 7A An isometric view of the eye and the eye-receiving device, which indicates the eyelid force vector of the positioning and holding device.

[0097] Figure 7C yes Figure 7A A side view of the eye and the eye-receiving device, the view having a force vector representing the force that holds the device under the eyelid.

[0098] Figure 7D It is an isometric view of a portion of the eye, in which the lower eyelid is partially removed to expose the space inside the eye. Figure 7A The receiving device.

[0099] Figure 7E yes Figure 7D The image shows a side view of the eye and the receiving device.

[0100] Figure 7F yes Figure 7A Rear view of the device.

[0101] Figure 7G yes Figure 7AThe image shows a top-view cross-sectional view of the receiving device, with the cross-section on a horizontal plane.

[0102] Figure 7H It is in contact with the sclera, which is the cross-section of the eyeball. Figure 7A An exploded cross-sectional view of the plate of the device.

[0103] Figure 8A This is a flowchart illustrating an example of the manufacturing process of a clinical use device according to an exemplary embodiment.

[0104] Figure 8B This is a diagram illustrating the performance attribute contributions of the connector and insert.

[0105] Figure 9A1 This is a front view of the receiving device, in which the plate is cut in a horizontal plane to expose a recess.

[0106] Figure 9A2 yes Figure 9A1 The front view of the device, in which the insert is aligned to be inserted into the recess in the plate.

[0107] Figure 9B yes Figure 9A2 The front view of the device, in which the insert is inserted into the plate.

[0108] Figure 10A This is a front view of the receiving device, in which plates are cut in a horizontal plane to expose recesses in the plates, and different inserts are aligned to be inserted into the recesses in each plate.

[0109] Figure 10B yes Figure 10A The front view of the receiving device, in which the insert is inserted into the plate.

[0110] Figure 11A This is a front view of an eye medication delivery system, illustrating the system's components.

[0111] Figure 11B yes Figure 11A A bottom view of the system.

[0112] Figure 12A This is a front view of an eye medication delivery system, in which a plate is cut in a horizontal plane to expose recesses in the plate.

[0113] Figure 12B yes Figure 12A A rear view of an eye medication delivery system, in which a plate is cut in a horizontal plane to expose recesses in the plate.

[0114] Figure 13A This is a front view of the receiving device.

[0115] Figure 13B yes Figure 13A A top view of the device, showing the recesses of the plate and the diaphragm of the sealing surface.

[0116] Figure 13C yes Figure 13B An example of a front view of the device, in which the plate is cut open to expose the interior of the recess.

[0117] Figure 14A This is a front view of the receiving device.

[0118] Figure 14B yes Figure 14A The image shows a bottom-view cross-sectional view of the receiving device, with the cross-section on a horizontal plane.

[0119] Figure 14C yes Figure 14A A frontal cross-sectional view of the receiving device, wherein the cross-section is in a vertical plane.

[0120] Figure 15A This is a front view of the receiving device.

[0121] Figure 15B yes Figure 15A A bottom view of the receiving device.

[0122] Figure 15C yes Figure 15A A partial cross-section of the plate of the receiving device shows a recess that is open on the back of the plate.

[0123] Figure 16A This is a front view of the receiving device.

[0124] Figure 16B It was rotated 180° Figure 16A A top view of the receiving device.

[0125] Figure 17A This is a front view of the receiving device.

[0126] Figure 17B yes Figure 17A Rear view of the receiving device.

[0127] Figure 18A This is a front view of the receiving device.

[0128] Figure 18B yes Figure 18A A top view of the receiving device.

[0129] Figure 18C yes Figure 18A A top view of the receiving device, in which the top portion of the plate is cut off.

[0130] Figure 19A , Figure 19B and Figure 19C These are the front, top, and rear views of the viewing device. The consecutive figures illustrate the device while maintaining its left-right orientation, rotating about the slender support member toward the observer in 90° increments.

[0131] Figure 19D , Figure 19E , Figure 19F and Figure 19H They are respectively along Figure 19A The cross-sectional views of lines AA, BB, CC and DD of the device.

[0132] Figure 19G yes Figure 19A An isometric view of a portion of the receiving device, wherein the plate is cut to show the recesses in the plate.

[0133] Figure 19I It can be placed in a receiving device (including Figures 19A to 19H An isometric view of an example of an insert (or medicine insert) in a receiving device.

[0134] Figure 20A This is a front view of the receiving device.

[0135] Figure 20B yes Figure 20A A cross-sectional view of the receiving device along line BB.

[0136] Figure 20C yes Figure 20A A cross-sectional view of the receiving device along line AA.

[0137] Figure 20D yes Figure 20A The front view of the receiving device is simplified so that no recesses appear in the plate.

[0138] Figure 20E Is it like this? Figure 20D The front view of the receiving device is shown, with shading added to show the open space 250 within the perimeter of the receiving device.

[0139] Figure 20F The eye-catching device has been removed. Figure 20F An open space.

[0140] Figure 20G It was rotated 45 degrees. Figure 20F A view of the open space.

[0141] Figures 21A to 21L An example of a plate with protrusions is shown.

[0142] Figure 22A This is a front view of the receiving device.

[0143] Figures 22B to 22E An example of a plate with protrusions is shown.

[0144] Figure 23A This is a front view of an example of a receiving device.

[0145] Figure 23B yes Figure 23A Rear view of the receiving device.

[0146] Figure 23C This is a front view of an example of a receiving device.

[0147] Figure 23D yes Figure 23C Rear view of the receiving device.

[0148] Figure 23E This is a front view of an example of a receiving device.

[0149] Figure 23F yes Figure 23F Rear view of the receiving device.

[0150] Figure 23G This is a front view of an example of a receiving device.

[0151] Figure 23H yes Figure 23G Rear view of the receiving device.

[0152] Figure 23I yes Figure 23H The cross-sectional view of the receiving device along AA.

[0153] Figure 24A This is a front view of the receiving device.

[0154] Figure 24B yes Figure 24A Rear view of the receiving device.

[0155] Figure 24C yes Figure 24A A cross-sectional view of the receiving device along line AA.

[0156] Figure 24D It can be placed in a receiving device (including Figures 24A to 24C An isometric view of an example of an insert (or medicine insert) in a receiving device shown in the figure.

[0157] Figure 25A It is a three-dimensional view of an open shell.

[0158] Figure 25B yes Figure 25A The image shows a side cross-sectional view of the open casing.

[0159] Figure 25C yes Figure 25A The image shows a perspective view of the casing, with the cover in the closed position.

[0160] Figure 25D yes Figure 25C The perspective view of the housing shown shows the port in the peeling strip covering the cover.

[0161] Figure 26A This is a perspective view of an example of an open housing for holding a receiving device.

[0162] Figure 26B This is a perspective view of an example of a closed housing for holding a receiving device (not shown).

[0163] Figure 26C This is a perspective view of an example of an open housing containing a receiving device that protrudes from the side of the receiver away from the compartment.

[0164] Figure 26D This is a perspective view of an example of an open housing that maintains proximity to the compartment and protrudes from the receiver.

[0165] Figure 27A This is a schematic diagram illustrating an example of a kit including a housing and a solution containing a receiving device (not shown).

[0166] Figure 27B This is a schematic diagram illustrating an example of the kit, in which a solution is applied to a receiving device (not shown) within the housing.

[0167] Figure 28A This is a graph showing the cumulative release of ciprofloxacin FB over time, and also shows the release distribution of the three components in the device insert in Table 7.

[0168] Figure 28B This is a graph showing the cumulative release of ciprofloxacin hydrochloride over time, and also shows the release distribution of the three components in the device insert in Table 7.

[0169] Figure 29A This is a graph showing the cumulative release of dexamethasone FB over time, and also shows the release distribution of the three components in the device insert in Table 8.

[0170] Figure 29B This is a graph showing the release time of dexamethasone phosphate control and the release distribution of the three components in the device insert shown in Table 8.

[0171] Figure 30 This is a graph showing the cumulative release of olopatadine FB over time, and also shows the release distribution of the three components in the device insert in Table 9.

[0172] Figure 31AThe graph shows the percentage of polyoxyethylene (polyox) released within 12 hours at 200,000 MW compared to the percentage of the initial polyoxyethylene (polyox) loading at 200,000 MW, and illustrates the effect of polyoxyethylene loading on polyoxyethylene release for 200,000 MW of polyoxyethylene.

[0173] Figure 31B The graph shows the percentage of ethylene oxide released within 12 hours (300,000 MW) compared to the percentage of the initial ethylene oxide loading (300,000 MW), and illustrates the effect of ethylene oxide loading on ethylene oxide release for 300,000 MW of ethylene oxide.

[0174] Figure 31C The graph shows the percentage of 100,000 MW of ethylene oxide released within 12 hours compared to the percentage of the initial 100,000 MW ethylene oxide loading, and illustrates the effect of ethylene oxide loading on ethylene oxide release for 100,000 MW of ethylene oxide.

[0175] Figure 31D This is a graph showing the percentage of polyethylene oxide released within 12 hours compared to the percentage of initial polyethylene oxide loading, and illustrating the effect of polyethylene oxide loading on polyethylene oxide release for various insert components.

[0176] Figure 32 This is a graph showing the cumulative percentage of ciprofloxacin FB released from the insert versus time, and also showing the cumulative percentage of ciprofloxacin released from the insert after 7 days in the device. Detailed Implementation

[0177] The following is a description of an example of a docking device.

[0178] The example eye-viewing device is configured to be placed inside the eye. The front portion of the device is the surface facing the eyelid. The rear portion of the device is the surface facing the sclera of the eye. The device can optionally be configured such that either the front or rear portion of the device faces the sclera of the eye.

[0179] Clinical details and illustrations of the physical geometry and measurements of the eye and eyelids.

[0180] Researchers studying the anatomy of the eye have described extensive anatomical data variability across the entire population.

[0181] Figure 1This is an isometric view of a three-dimensional (3D) "CAD" model of an emmetropic eyeball with normal focus (normal vision), which identifies the sagittal (vertical) plane, lateral (horizontal) plane, and optical axis as spatial references and shows the degrees of freedom. The model includes the eyeball, outer cornea, and outer scleral surface. The sclera, or scleral surface, is the white outer layer of the eyeball. The sclera is the opaque, fibrous, tough, protective outer layer of the eye ("the white of the eye"), continuous with the cornea at the front of the eyeball and with the sheath covering the optic nerve at the back of the eye. Clinically defined sections (based on which clinical imaging measurements were performed across the entire population) and indicators of optical axis and kinematic axis rotation appear with the eyeball; the optical axis defines the focal length, and the kinematic axis rotation indicators define the eye's motor capabilities and the degrees of freedom of human eyeball fixation. The anatomical model is derived from representative clinically published data. The retina is a thin layer of tissue located on the inner side of the eye, near the optic nerve. The purpose of the retina is to receive light focused by the lens, convert the light into neural signals, and send these signals to the brain for visual recognition.

[0182] The eyeball 090 includes a cornea 101 and a sclera 102, showing the outer surface boundary of an emmetropic eye. The cornea 101 is an optical visual focusing element comprising a spherical geometry with a historically classic outer radius measurement of 7.7 mm and a diameter of approximately 11.7 mm, which optically defines an optical “focusing” axis (“X”) 105 that projects an image onto the retina. A sagittal (vertical) plane 103 and a transverse (horizontal) plane 104 are perpendicular to each other and thus intersect along the optical axis (“X”) 105.

[0183] Using the "6DOF" convention, a local origin, three axes, and a centerline section are defined. The vertical axis ("Z") 106 is perpendicular to the horizontal axis ("Y") 107 and the optical axis ("X") 105. The horizontal axis ("Y") 107 is also perpendicular to the optical axis ("X"). The defined axes 105, 106, and 107 intersect individually at the local origin 100 (the nominal center point of the visual eye's anatomical structure). The sagittal plane (vertical meridian) 103 is formed by the vertical axis 106 and the optical axis 105. The transverse plane (horizontal meridian) 104 is formed by the horizontal axis 107 and the optical axis 105. The sagittal plane 103 is perpendicular to the transverse plane 104, which intersects the optical axis 105.

[0184] Figure 1The rotational movement capabilities of the eyeball 090, constrained by eyeball fixation and muscle movement anatomy (not shown), are also illustrated. Vertical axis rotation arrow 108 describes the left visual input effect 110 and right visual input effect 109 for eyeball rotation about the vertical (“Z”) axis 106. Horizontal rotation arrow 111 describes the upper visual input effect 112 and lower visual input effect 113 for eyeball rotation about the horizontal (“Y”) axis 107. Taken together, these gaze rotations define two rotational degrees of freedom for the eyeball 090 about the origin 100, sufficient to observe any object within the field of view.

[0185] While the internal optical focusing structure of the eyeball has been shown to be relatively uniform, the external width and optical axis length of the eyeball have been shown to exhibit wide variability. This range of variability defines the curvature and surface shape of the non-optical scleral surface and adjacent supporting tissues.

[0186] Figure 2A This is an isometric view of the eyeball 091, including the cornea 101 and sclera 102, showing the outer surface boundary of an emmetropic eye. (As shown...) Figure 1 The transverse (horizontal) plane 104 shown defines the location of the eyeball cross-section in the remaining figures. Figure 2A The eyeballs shown represent normal (emergent) eyes, and their measurements are shown in Table 1.

[0187] Figure 2B yes Figure 2A The figure shows a transverse (horizontal) sectional view of the emmetropic eyeball 091. This figure illustrates the internal optical anatomy of the eye, including the lens capsule and iris 114, cornea 101, and sclera 102. The optical axial length 116 of the example eyeball 091 is 23.5 mm, and the transverse (horizontal) width 115 is 24.2 mm, representing the average values ​​of an "idealized" clinical eye model.

[0188] Figure 2C This is a transverse (horizontal) cross-sectional view of a myopic (near-vision) eyeball 092, which has an optical axial length of 26 mm 116 and a transverse (horizontal) width of 24.2 mm 115, representing the average value of a clinical myopic eye model.

[0189] Figure 2D This is a transverse (horizontal) cross-sectional view of a hyperopic (far-vision) eyeball 093, with an optical axis length of 21 mm (116) and a transverse (horizontal) width of 24.2 mm (115), representing the average value of a clinical hyperopic eye model.

[0190] Figure 2E This is an isometric view of the largest volume eyeball 094, which has an optical axial length of 26 mm 116 and a lateral (horizontal) width of 27 mm 115.

[0191] Figure 2F This is a transverse (horizontal) cross-sectional view of the smallest volume eyeball 095, which has an optical axial length of 20 mm 116 and a transverse (horizontal) width of 21 mm 115.

[0192] These measurements are shown in the illustrative diagram to compare and understand the meridian in the transverse (horizontal) plane cross-section. Figure 2A The range of surface and curve shape differences seen at 104) (see Bekerman, I; Gottlieb, P; & Vaiman, M; (2014) "Variations in Eyeball Diameters of the Healthy Adults", Journal of Ophthalmology, Vol. 2014, Article ID 503645, p. 5, 2014, the entire contents of which are incorporated herein by reference).

[0193] Table 1

[0194] Figure 3A and Figure 3B as well as Figures 4A to 4F Clinical data and anatomical differences in eyelid size, shape, depth to the fornix, width, and canthal-canthal opening in the entire population are illustrated based on studies in publications on this subject. Figures follow. Figure 1 The "6DOF" naming convention was introduced and applied in [the context of the document / instructions]. Figure 2A and Figure 2B The nominal emmetropic clinical corneal and scleral measurements used are presented to show the mean and range of variability of eyelid data, as described in the clinical studies in the publications.

[0195] Figure 3A This is an isometric view of a representative eyeball 125 without specific parameters. Geometric control values ​​are ideal averages of representative clinical data from the cited publications. The figure includes the cornea 101 and sclera 102, the upper eyelid 119, the lower eyelid 118, the conjunctival tissue 117, the two canthi (corners) 120 where the upper and lower eyelids meet, and the palpebral fissure width (“PFW”) 122 between the canthi 120 along a transverse (horizontal) plane 104, which defines the geometry of the upper eyelid 119 and the lower eyelid 118.

[0196] like Figure 1 In the middle, the sagittal (vertical) plane 103 and the transverse (horizontal) plane 104 are perpendicular to each other and are located and intersect at the optical axis 105 of the cornea 101.

[0197] Figure 3B It has Figure 3A A side view of the eyeball 125 illustrating the eyelid anatomy, which also shows the cornea 101, sclera 102, upper eyelid 119 and lower eyelid 118, conjunctival tissue 117, and one of the two canthi 120. The view also illustrates the clinical measurement location 121 for palpebral fissure height (“PFH”), which measures the vertical eyelid space across the cornea.

[0198] Table 2 summarizes the differences in eyelid width and lower eyelid depth across many populations and cultures. Table 2 presents the mean, minimum, and maximum general clinical measurements of palpebral fissure width from corner to corner along the transverse plane and the mean, minimum, and maximum values ​​of lower eyelid measurements along the vertical plane of both upper eyelid UFD and lower eyelid LFD depths, used to describe the range of anatomical differences in populations. Figures 4A to 4F An example eyeball with eyelids is shown, illustrating the data summarized in Table 2.

[0199] Figure 4A This is a frontal view of the eyeball in Table 1, perpendicular to the sagittal plane 103 and the transverse plane 104, showing an eyelid 096 representing a person aged 20 to 30 years. It is shown as a cross-section in a vertical plane parallel to the intermediate plane (sagittal section). The eyeball 096 has a cornea 101, sclera 102, upper eyelid 119, lower eyelid 118, conjunctival tissue 117, two canthi (corners) 120 at the palpebral fissure where the upper and lower eyelids meet, and a PFW 122. Example eyeball 096 in... Figure 4A The section is shown as having a PFW of 30 mm, and the cross-section is shown in a vertical plane.

[0200] Figure 4B yes Figure 4A The image shows a cross-sectional view of the eyeball 096. Figure 4B The fornix depth 123 of the upper eyelid (119) is 16.2 mm and the fornix depth 124 of the lower eyelid (118) is 11.5 mm.

[0201] Figure 4C This is a front view of eyeball 097 with the minimum observed PFW as shown in Table 2, with the cross-section shown in a vertical plane. Example eyeball 097 has a PFW of 27 mm.

[0202] Figure 4D yes Figure 4C A cross-sectional view of the eyeball (097). Figure 4D The fornix depth 123 of the upper eyelid (119) is 13.8 mm and the fornix depth 124 of the lower eyelid (118) is 9.9 mm.

[0203] Figure 4EThis is a frontal view of the eyeball 098 representing the observed maximum PFW 122, maximum upper eyelid depth (mean) (“UFD”), and maximum lower eyelid depth (mean) (“LFD”) of 37 mm, as provided in Table 2.

[0204] Figure 4F yes Figure 4E A cross-sectional view of the eyeball and eyelids.

[0205] Table 2

[0206] “PFW” = Palpebral fissure width (average) “UFD” = Upper eyelid depth (average) “LFD” = Lower eyelid depth (average)

[0207] Clinical details and illustrations of the dynamics of the eye and eyelids and the observed forces.

[0208] Researchers studying the kinematics of the eye's anatomy have described rapid and frequent eye movements and eyelid movements in individuals. The following descriptions, summary tables, and figures illustrate clinical observations, measurements, and visual acuity as background to aid understanding of the descriptions below. Clinical observations include measurements of saccades, saccades during gaze, blinking, and eyelid tension.

[0209] Scan

[0210] Salivary eye movements are rapid, have a nominal constant intensity value, and last for milliseconds; they are a function of angular displacement. Vision requires continuous movement of the eye's anatomy to stimulate retinal cells. Therefore, the eyeball is not usually completely still.

[0211] The degree of surface movement (called surface translation) of the sclera of an eyeball with a known radius (half the diameter) can be calculated from the angle of eye movement. The formula used to determine surface translation is eye radius (r) multiplied by the angle of movement (in degrees θ) multiplied by π divided by 180 or (r × θ × π) ÷ 180. As an example, an eyeball with a diameter of 24 mm will have a radius of 12 mm. If the eyeball moves by 5 degrees, the surface translation will be (12 mm × 5 × 3.14) / 180 or 1.05 mm.

[0212] Table 3 below summarizes the scleral surface translation based on clinical saccade eye movement studies on an eyeball with a diameter of 24 mm (radius of 12 mm): Macroscopic eye movements within the field of vision; and Gaze saccades across image types (micro-angle eye movements).

[0213] See Robinson DA; (1964) “The Mechanics of Human Saccadic Eye Movement” J. Physiol

[1964] 174 pp. 245-264 and Castelhano, M; & Henderson, J (2008) “Stable Individual Differences Across Images in Human Saccadic Eye Movements” (Canadian Journal of Experimental Psychology: 2008, Vol. 62, No. 1, pp. 1-14).

[0214] Table 3 summarizes studies considering macroscopic non-fixed scanning angle displacements in the range of 5° to 40° for an eyeball with a nominal thickness cross-section of 12 mm and an outer surface radius of 102. The displacement of the outer surface curvature length is defined by angular scanning values ​​of 5°, 10°, 15°, 20°, 25°, 30°, 35°, and 40°. Calculated surface displacement values ​​representing the expected surface displacement for each macroscopic scanning angle are provided.

[0215] Table 3 also summarizes the results of a study on the spectral displacement of the eyeball under gaze microscans with a nominal thickness of 12 mm on the outer surface at angular scan values ​​of 1.4°, 2.5°, and 3.3°. The calculated scleral surface translation for each gaze type is shown in Table 3.

[0216] The summary of continuous saccadic movements and time in Table 3 relates to devices that will be placed under the eyelids or within the "conjunctival sac," and is therefore affected by this dynamic, rapid-motion environment.

[0217] Table 3

[0218] blink

[0219] Blinking is the movement of the eyelids wiping the surface of the eye. A blink closes the palpebral fissure height (“PFH”) to 25% to 100% within approximately 0.1 seconds, with prolonged blinks lasting at least 1 / 2 second. Eyelid movement is the translation of the inner eyelid relative to the surface of the eye's anatomy, typically along the vertical meridian of the eye. The eyelids usually move within a range of 25% to 100% (at 100%, “PFH” = 0).

[0220] Table 4 summarizes information about blink rate and blinking action.

[0221] Table 4

[0222] The duration of a blink (in seconds) is 0.1 (80%-95%) / 0.5 (5%-15%).

[0223] eyelid tension

[0224] Eyelid forces important for holding devices intended to be placed under the eyelid have been measured in the posterior-anterior (PA), nasal, and temporal directions. These forces represent the lower eyelid anatomical properties of the device's holding ability. Relevant factors are summarized in Tables 5 and 6.

[0225] Table 5

[0226] Average anterior-posterior (PA) eyelid tension by age and sex

[0227] Table 6

[0228] Eyelid tension by location in the "young" age group

[0229] A set of interactive elements is described that work together to provide the user with an adaptive eye-viewing device that remains stable and comfortable when placed under the eyelid. The unique challenges in the field of ocular anatomy, as well as the anatomical differences, degrees of movement, and forces, provide a specific environment for this eye-viewing device.

[0230] This description illustrates various aspects of the receiving device, including its adaptive characteristics. For further clarity, features of the receiving device can be isolated from the device itself. Features can be incorporated into the receiving device.

[0231] A system including an eye-connecting device is described, which is adapted to the variability of eye anatomy, is comfortable within the eye space, is positioned and stabilized within the eye anatomy, resists forces from eyeball and eyelid movements, and retains tear fluid.

[0232] Devices for use on the upper and lower eyelids are described. The devices are adaptable. The description of the devices is not intended to be a constraint or limitation in any way. In particular, alternative anatomical placement locations may exist for any of the devices described.

[0233] Materials used for the eye-catching device.

[0234] Advantageously, the composition and properties of the receiving device enable translation along multiple degrees of freedom.

[0235] The following materials are advantageous, which help to transform from a planar "manufactured" structure or a manufactured structure shape that is transformed from an intermediate part into a device that is compatible with the patient when placed within the anatomy of the eye to perform its purpose.

[0236] The eyepiece can be made from materials that provide adaptability to the constructed device. Anatomically compatible combinations of primary and composite materials can be used to fabricate the eyepiece, including injection-molded materials.

[0237] Materials that can be used to make contact devices with adaptive properties may include, but are not limited to, the following (alone or in combination or as a composite): metals, polymers, composites, thermoplastic polymers, thermosetting polymers, thermoplastic elastomers, thermosetting elastomers, metal compositions or pure elements (such as carbon nanotubes) or combinations thereof.

[0238] Suitable materials may be, but need not be, hydrophilic. Any hydrophilic material used in devices under the eyelids, on the cornea, or on the sclera is well-defined and characterized by contact lens materials practice and numerous ophthalmic clinical publications.

[0239] A suitable, low-cost injectable material is a class of ethyl vinyl acetate (EVA) thermoplastic copolymers, which have a proven history of use in anatomical contact drug delivery systems, providing superior patient comfort while remaining in the ocular space. These materials possess hydrophilic properties compatible with ocular anatomy, provide appropriate stiffness and flexural modulus for translation during adaptation, and offer crucial tear wetting properties within the ocular anatomy for compatibility and comfort.

[0240] The surface finish of the receiving device.

[0241] The surface finish of an optical device can include injection-molded surfaces with optical quality finish.

[0242] Compositions, materials, and methods known in the art can be used. These compositions, materials, and methods can be selected to increase patient comfort and device retention while minimizing user discomfort.

[0243] Manufacturing method.

[0244] The manufacture and validation of receiving devices and transportation mechanisms require process steps that include process losses, which impact costs. A manufacturing process is described in U.S. Patent No. 9,937,073 (de Juan et al.), the entire teachings of which are incorporated herein by reference.

[0245] There are many manufacturing methods that can be used to produce the device. One example that can be used is to select an injection molding material that meets the material properties and use the injection molding process to fabricate the device, and then apply a mechanical assembly method to place the drug delivery insert into the receiving device.

[0246] The receiving device is not limited to devices made by any particular method. Manufacturing process steps can be followed as an example. Figure 8A Flowchart in the middle: The receiving device is injection molded; Generate a drug insert to fit the recess of the eyepiece device; Optionally, a drug or another substance may be added; and The insert is assembled with the contact device to create a device for clinical use.

[0247] This example is a simple, scalable, and low-cost process, thus providing a general framework for following. Figure 8A The manufacturing process steps and provided Figure 8B The performance properties of the connector and insert are shown in the figure.

[0248] The receiving device may be formed wholly or partially from a pharmaceutically active agent blended with other materials that enable the delivery of the pharmaceutically active agent from the receiving device. As an example, the receiving device may be a plate, or may include a plate formed wholly or partially from a material comprising the pharmaceutically active agent.

[0249] The receiving device is provided as a structural example.

[0250] An eye-mounting device for placement under the eyelid is described and depicted in the figures illustrating features that can be included in the device. The description and figures include multiple features connected together, for example, one or more plates connected to an elongated support member. The features shown are connected for illustrative purposes and not as limitations. An eye-mounting device for placement under the eyelid may be a plate not connected to other features. Therefore, it should be understood that each plate illustrated herein can be used as an eye-mounting device without any other features attached to the plate. Alternatively, one or more plates may be connected to a support member or an elongated support member. The connection of one or more plates to a support member or elongated support member is not limited to any configuration described or shown in a particular figure.

[0251] The normal tear volume is considered to be approximately 7.2 µl. The tear volume in each eye can be greater or less than normal. It should be understood that the eye-connecting device shown in the figures or described herein provides an open space of 250° when placed under the eyelid. Eyes with the eye-connecting device placed under the eyelid typically have a larger tear volume than eyes without the device.

[0252] Increased tear volume can promote a longer residence time of drugs in the ocular anatomy. Compared to ocular drop delivery systems, drugs will experience a longer residence time in ocular tissues. Many drug solubility barriers can be overcome by increasing drug delivery in accordance with the increased tear residence time.

[0253] Figure 5A , Figure 5B and Figure 5C These are isometric views, bottom views, and front views of an example of an adaptive eye-receiving device 299 for the eye. The eye-receiving device 299 includes an elongated support member 301, plates 511 and 521 connected close to each end of the support member and substantially coplanar with the support member, and plates 531, 541, and 551 connected between plates 511 and 521 and connected to the support member. The eye-receiving device can be placed under the eyelid in various positions and orientations. By way of example, and not limitation, the eye-receiving device can be placed under the eyelid with the elongated support member facing the fornix. By way of another example, and not limitation, the eye-receiving device can be placed under the eyelid with the plates facing the fornix. Once placed under the eyelid, the eye-receiving device can self-position and can rotate about its horizontal axis. Plates 511 and 521 are configured to be positioned adjacent to the corner of the eye. The plates are configured to be adapted to the anatomy of the eye. Plates 531, 541, and 551 are substantially coplanar with the support member and plates 511 and 521. The plate has a rear surface, which may have at least one protrusion having a convex contact surface. The eye-contacting device may include a substance to be delivered to the eye, such as a medication. An elongated support member 301 extends toward each corner of the eye when in place. The elongated support member may be made of a flexible material. The elongated support member 301 may include an arch 303. The eye-contacting device may have an elongated support member whose cross-section is variable along its length (see [link to relevant documentation]). Figure 19A ).

[0254] Individually or consistently, the adaptability of each plate of the eye-connecting device 299 provides an adaptive device that can be adjusted to the differences in eye anatomy, which is advantageous.

[0255] Figure 5A The example eye-mount 299 illustrates the presence of an open space 250 surrounding the eye-mount 299. The open space 250 allows each plate and other feature of the eye-mount 299 multiple degrees of freedom of movement relative to each other. The eye-mount 299 in the eye produces a larger tear volume than an eye without an eye-mount. The open space 250, along with the offset space between the sclera and the posterior surface of the plate, contributes to achieving the larger tear volume resulting from the insertion of the eye-mount into the eye. The elongated support member 301 itself can be formed of a flexible material, thus providing its own degrees of freedom, further providing an adaptive eye-mount.

[0256] When in the eye, plates 511 and 521 can stabilize the eye contact device.

[0257] exist Figure 5A and Figure 5C In the middle, the connecting device 299 includes flexible connectors 411, 431, 441, 451 and 421 for connecting the plate to the support member.

[0258] Figure 5B A mounting device with a planar curved surface 300 is shown to illustrate the projected shape or height of the plate in the example mounting device 299. The planar curved surface 300 appears... Figure 5B The example shown is merely for illustrative purposes.

[0259] As the eyelid approaches the 120° junction of the inner canthus (located at the nasal and temporal position), it exhibits both a reduced volume and a reduced depth from the fornix to the palpebral fissure. See [reference needed]. Figure 3A and Figure 3B To achieve a comfortable design fit and device retention, it is advantageous that plates 511 and 521 are placed closer to the corner of the eye, connected to an elongated support member 301 compatible with the dome, and the shape, size, and profile of the plates are adjusted to fit within the volume and depth of the eyelid.

[0260] exist Figure 5B In the example receiving device 299, the exemplary planar curved surface 300 is best described as follows: Starting from plate 511, the plate generally follows the planar curved surface 300 as shown, from plate 511... Figure 5B Starting from the left side, the height across plate 531 increases, reaching a peak at plate 541 (plate 541 is shown at the center in the device 299), then the height across plate 531 decreases, returning to a point where the height decreases along plate 521 (plate 521 is shown at the center). Figure 5B (The right side of the middle).

[0261] The radius of curvature of 300 can be adjusted to be greater than that in Figure 5B The steeper (smaller radius) or flatter (larger radius) surfaces, as illustrated, provide more or less volume for plates 531, 541, and 551, and alter the overall device height along the path of curve 300. The plate volume and the overall device height determine the offset position of the eyelid relative to the sclera during insertion, when the eyelid is the surface furthest from the sclera.

[0262] Device 299, comprising a plate, a flexible connector, and an elongated support member made of flexible material, provides an eye-connecting device that can be inserted under the eyelid and adjusted and adapted independently or uniformly to the differences in eye anatomy and structure.

[0263] The curved shape and height of the eyelid device 300 can be adjusted to take into account the user's eyelid tension and eyelid shape. Such adjustments can provide the eyelid device with an aesthetically acceptable appearance when inserted under the eyelid, in order to achieve successful adoption of the eyelid device.

[0264] Reception devices (such as) Figures 5A to 5C The plate in the device illustrated herein may include a front surface on the opposite side of the plate from the rear surface, and the front surface may optionally have at least one protrusion having a convex contact surface for contacting the sclera of the eye and providing offset space between the sclera and the front surface of the plate, such that the eye-connecting device can be inserted with the front surface facing the sclera (see, for example...). Figures 18A to 18C (Example 591). The eye-viewing device can be placed in the eye, wherein the posterior or anterior surface of the device faces the sclera.

[0265] Figure 5D yes Figure 5A An isometric view of the viewing device. (For illustration) Figures 5A to 5C The adaptability of the example receiving device in the example, Figure 5D The receiving device 299 is shown, in which an element that is not actually present in the device but is added for illustrative purposes is added. Figure 5D The axis of rotation is shown in the figure. Figure 5D Arrows are provided to illustrate multiple degrees of freedom, demonstrating the adaptability of the receiver 299. Figure 5D In this example, the rotational degrees of freedom of the plates are illustrated by rotational direction "arrows" associated with the inserted rotational axes added for each plate. The degrees of freedom of the slender support members are also indicated in this example.

[0266] By reference Figures 6A to 6G Further description of the disclosed viewing device, Figures 6A to 6G Examples of an elongated support member 301 that can be used in an adaptive connection device and examples of connection devices are shown. The exemplary elongated support member 301 can have different constructions.

[0267] Figure 6A An example is shown: a slender support member 301 without an arch.

[0268] like Figure 6B As illustrated, the elongated support member 301 may have a rectangular cross-section 306. The cross-section of the elongated support member 301 may vary along the length of the elongated support member (see example...). Figures 19A to 19CThe device 800 illustrated in the diagram. The cross-section may be rounded, providing a non-damaging surface with a general thickness of about 0.2 mm to about 1.5 mm and a height of about 0.45 mm to 2.25 mm. The member 301 may follow a sweep curve 304 across the width of the device and may include an arch 303, which may be located in the general region of the midpoint of the member 301. The arch 303 may be centrally positioned within the structure 301.

[0269] exist Figure 6B In the middle, the peak of arch 303 is located at approximately twice the length of the vertical cross-section 306, and approximately at the midpoint of the device. Arch 303 may be approximately 15% of the overall horizontal width of member 301.

[0270] For example Figure 6A and Figure 6B As shown, the elongated support member of the eye-connecting device can be manufactured with or without an arch 303. When an arch is present, the lower part 302 of the arch 303 may include accessories for manufacturing assistance. Placing the accessories or manufacturing aids on the lower part 302 of the arch 303, away from and without interfering with the placement of the eye-connecting device under the eyelid, can minimize the negative clinical impact on the performance of the eye-connecting device.

[0271] Manufacturing aids can be gates for injection molding, injection casting, or solution casting using methods and materials in one or more stages, including but not limited to: thermoplastic polymers, thermoset polymers, in-situ polymerization, drug-polymer composite structures, and coatings. Manufacturing aids can also be processing attachments for manufacturing processes and / or high-speed automation. Additionally, manufacturing aids can be positional features for subsequent component fabrication processes, lamination, composite assembly, coating, drug insertion, and / or drug infusion via multiple process steps. Manufacturing aids can also be removable identification tags for patients or physicians, with or without embedded electronically scannable identification labels or medical device regulatory-approved scannable device barcode identifiers.

[0272] Figure 6C An example of the rotational capability of an elongated support member 301, which contributes to the adaptability of the receiving device, is illustrated. A horizontal (vertically extending) axis 001 and a vertical (perpendicular to the horizontal plane) axis 003 define a local origin 999 for the elongated support member 301. An arch 303 provides a rotational feature, and each swept arc 304 has a torsional capability about this rotational feature, as defined by the axis 004 and torsional direction arrow 008 at one end and the axis 006 and torsional direction arrow 009 at the other end.

[0273] Figure 6DAn eye-connecting device 270 is illustrated, having plates 511, 521 connected near each end of an elongated support member, each of the plates 511, 521 being configured to be positioned adjacent to the corner of the eye. The plates 511, 521 of the eye-connecting device 270 are adaptable to the anatomy of the eye. The eye-connecting device 270 is an example of a device that does not include plates other than those connected near each end of the elongated support member 301.

[0274] Slender support member 301 appears Figure 6D In the middle, there is an arch 303 and a swept arc 304. The flexible connector 411 is connected to the elongated support member at an acute angle 1125 and connects the plate 511 to the elongated support member, and similarly, at the other end of the elongated support member, the flexible connector 421 is at an acute angle to the elongated support member, thereby connecting the plate 521 to the elongated support member.

[0275] Typically, flexible connectors can form an angle ranging from less than 90 degrees to greater than 180 degrees with elongated support members, thereby connecting the elongated support members to the board, wherein the elongated support members are substantially coplanar with the surface of the board.

[0276] Figure 6E Examples Figure 6D The image shows an isometric front view of the eye-connecting device 270, in which plates 511, 521 and flexible connectors 411, 421 are attached to an elongated support member 301. Vertical axes, facial axes, and torsional axes (which are not part of the device and are provided for illustration) and associated rotational arrows indicate the degrees of freedom of movement of the plates relative to the elongated support member, which allow for adaptation to the anatomy of the eye.

[0277] exist Figure 6E The diagram illustrates the rotational capabilities of plates 511, 521 and connecting elements 411, 421 relative to the elongated support member 301. Point 998 on the flexible connector 411 (the element exemplified on the left) provides a reference point for the adaptive movement of connector 411 and plate 511 at intersecting axis 011, horizontal axis 012, and vertical “torsion” axis 013. Directional arrow 015 indicates the location and position of plate 511 and flexible connector 411 relative to the sweeping arc 304 about axis 011, arrow 016 indicates the movement about axis 012, and arrow 017 indicates the movement about axis 013. Point 997 on the flexible connector 421 (the element exemplified on the right) provides a reference point for the adaptive movement of connector 421 and plate 521 at intersecting axis 021, horizontal axis 022, and vertical “torsion” axis 023. Directional arrow 025 indicates the location and position of board 521 and connector 421 relative to sweep arc 304 about axis 021, arrow 026 indicates the movement about axis 022, and arrow 027 indicates the movement about axis 023.

[0278] Figure 6F An example is shown of an eye-receiving device 280 having plates 531, 541, and 551, which are adaptable to the anatomy of the eye and connected to an elongated support member 301 via flexible connectors 431, 441, and 451. It can be noted that, with... Figure 6E Compared to plates 511 and 521, plates 531 and 551 are connected to the ends of the slender support members further away.

[0279] exist Figure 6F In the diagram, an elongated support member 301 is shown with an arch and a swept arc, and flexible connectors 431, 441, and 451 extend perpendicular to the curvature of the elongated support member to engage plates 531, 541, and 551, respectively. Connector 441 and plate 541 in the connection device 280 are centrally located and attached to the top of the arch of the elongated support member 301. Alternatively, connector 441 and plate 551 may be located in a non-central position, and as shown... Figure 6A As shown, the arch may not be present. It should be understood that any features shown in the figures (such as the vertical extension of the connector) are merely illustrative examples.

[0280] Figure 6G This is an isometric front view illustrating plates 531, 541, 551 and connectors 431, 441, 451 attached to the elongated support member 301 of the eye-connecting device 280. The vertical axis, facial axis, and torsional axis, along with the associated rotation arrows, define the degrees of freedom of movement of the plates relative to the elongated support member in the device 280 adapted to the anatomy of the eye.

[0281] Figure 6G The rotational capabilities of plates 531, 541, 551 and flexible connectors 431, 441, 451 relative to the elongated support member 301 are also illustrated.

[0282] An eye-connecting device placed within the anatomical structure of the eye.

[0283] Adaptive eye-connecting devices with multiple degrees of freedom will be further described by illustrating eye-connecting devices in the eye. The figures used in the description and association are not intended to be limiting. For example, while an example of an eye-connecting device may be shown located under the lower eyelid of an emmetropic eye, the same eye-connecting device may alternatively be shown under the upper eyelid of an emmetropic eye or under the upper or lower eyelid of an eye with myopia or hyperopia. As another example, an example of an eye-connecting device may be shown in one orientation, but the eye-connecting device may be in different orientations within the eye. Similarly, and as another example, an eye-connecting device may be shown in a position under the eyelid, but its shown position under the eyelid is not a limitation on where the eye-connecting device can be placed under the eyelid or where it can be moved.

[0284] When placed in the eye space, the disclosed optical device self-adjusts to fit and conform to the anatomy of the eye. The disclosed eye-connecting device can continuously adjust and self-correct to adapt to possible variations in non-corneal eye anatomy and to contact any element or group of elements of the eye-connecting device in any configuration due to visual movement.

[0285] Figure 7A This is an isometric front view of a portion of the eye 125, illustrating the placement of the eye-receiving device 126 below the lower eyelid 118. Figure 7A In this case, the lower eyelid has been partially removed to expose the device that is placed and positioned, oriented towards the fornix of the eye along with a slender support member. The engagement of the inner surface of the eyelid with the eye-connecting device can be negatively affected by eyelid changes such as ptosis. Ptosis is the natural conjunctival sac space within which part of the eye-connecting device can reside. The eye-connecting device 126 is adaptive and can engage with eyelids that are enlarged, loose, or ptosis. Typically, the eyelids of people over 50 years of age, who are most affected by eye diseases, may have larger conjunctival sacs for the placement of the eye-connecting device. Figure 7A The eye-connecting device shown has degrees of freedom that allow it to be adjusted and adapted to the surrounding eye surface and fit within it. A portion of the elongated support member is visible due to an eyelid incision spanning the width of the eye-connecting device, illustrating an example of the placement of the eye-connecting device in which the elongated support member is oriented toward the fornix of the eye.

[0286] Plates 511 and 521 (positioned adjacent to the corner of the eye 120 and connected to the elongated support member 301) are both adapted by rotation to mate with both the eyelid 118 and the partial scleral surface 102 across the eyelid interaction surface (partially removed). Plates 531, 541, and 551, connected to the elongated support member 301, are adapted by rotation to mate with both the eyelid 118 and the partial scleral surface 102 across the eyelid interaction surface (partially removed). Figure 7A The open space 250 shown, within the constraints of the eye-contact device and defined by the eyelid and scleral surfaces, provides additional space to retain tears, thereby contributing to a larger tear volume.

[0287] The plate's function is to guide the natural eyelid force and tension through the eye-receiving device in a balanced manner, keeping the device positioned under the eyelid to minimize the surface contact area against the dynamic effects of the saccadic surface.

[0288] As an example, plates 531, 541, and 551 have sufficient mass and height to correspond with plates 511 and 521, and these plates are configured to be positioned adjacent to the corner of the eye to properly interact with the eyelid along its span. This arrangement causes the device to behave as if it were a single unit, resulting in the device being comfortable in the eye and able to accommodate the naturally reduced eyelid tension due to tissue elasticity and distance from the corner of the eye.

[0289] exist Figure 7B In the image, the eyeball 125 and the eye-connecting device 126 are shown in an isometric view (see [reference]). Figure 7A The view includes the cornea 101, sclera 102, lower eyelid 118, and canthus 120. The lower eyelid 118 is centrally cut to expose the eye-connecting device 126. An elongated support member 301 is shown adapted adjacent to the dome. An arch 303 rises upward from the dome along the surface of the sclera 102, thus adapting to the optical anatomy inside and around the arch 303. Plates 511, 521 adjacent to the canthus of the eye 120 are moved and rotated to mate with the eyelid 118 and the surface of the sclera 102. Plates 531, 541, 551 connected to the elongated support member 301 are moved and rotated to mate across the eyelid ( Figure 7B The surfaces of the eyelid 118 and sclera 102 (which are removed from the center) are both. Eyelid force direction vector arrow 062 indicates that the lower eyelid force is applied downwards and centrally on plate 521. Eyelid force direction vector arrow 061 also indicates that the lower eyelid force is applied downwards and centrally on plate 511. The eyelid pressure on each plate adjacent to the corner of the eye (511 and 521), which generally points towards the vertical meridian and conjunctival fornix, results in a self-centering ability within the central conjunctival sac of the eyelid.

[0290] Figure 7B The arrow 061, showing the direction vector of eyelid force, indicates that the force applied downward and centrally to the fornix and vertical meridian anatomy on plate 511. The force applied to the eyelid device 126 is a result of the eyelid tension and volume at the corner of eyelid 118 to the eyelid cross-section of plate 511, including the conjunctival sac "drooping" effect where the inner surface 018 of the eyelid engages with plate 511 when the incision in this section extends towards the vertical meridian (eyelid extension not shown). Figure 7B As seen in the image, the eyelid force direction vector arrow 062 indicates that the lower eyelid force is applied downward and centrally on plate 521 towards the fornix and also towards the vertical meridian anatomical structure, as a force applied to the eye contact device 126. The applied force is a result of the eyelid tension and volume from the corner of the eye 120 to the eyelid cross section 118 of plate 521, including the eyelid "drooping" effect of the inner surface of the eyelid engaging with plate 521. The central eyelid drooping and the eyelid pressure on the plate closest to the vertical meridian, generally pointing towards the conjunctival fornix, create a holding capacity, i.e., resistance to ejection from saccadic eye movements.

[0291] Figure 7C The span of the eyelid above the sac 018 under the eyelid in the central part of the device 126 and the eyelid sac in contact with the device, as well as the pressure of the eyelid sac tissue on the device below. Figure 7C The eyelid force direction vector 060 indicates that when the inner surface of the eyelid 018 accommodates plate 541 (and all other plates) within the "conjunctival sac," the eyelid force is located at plate 541 and arch 303 ( Figure 7B The downward and central application is applied to the eyelid 118. The eyelid 118 is illustrated as a cross-sectional view at the central pass-through line of the central plate 541 of the eye-receiving device. Figure 7C The middle section shows the view on the right. Figure 7B The view includes an eyeball 125 and an eye-connecting device 126, comprising a cornea 101, a sclera 102, a lower eyelid 118, and a canthus 120. The lower eyelid 118 is centrally cut to expose the fitted eye-connecting device 126. An elongated support member 301 is shown positioned and adapted under the eyelid, oriented towards the fornix.

[0292] Figure 7D It is an isometric view of a portion of the eye, in which the lower eyelid is partially removed to expose the space inside the eye. Figure 7A The receiving device. In Figure 7D In the middle, the eye-receiving device is oriented so that the plate faces the dome of the eye.

[0293] Figure 7E yes Figure 7D The image shows a side view of the eye and the receiving device.

[0294] exist Figure 7F The image shows the eye-connecting device 126 as viewed from behind the eye. All components are adaptive and have the ability to... Figures 7A to 7C The "degrees of freedom" capability appears in the design, and the open space 250 allows for the movement of the features of the eye-viewing device 126. Plates 511, 521 and plates 531, 541, 551 are respectively attached to an elongated support member. Plates 511 and 521 are adjacent to the corners of the eyes and connected to the elongated support member 301 via flexible connectors 411 and 421, respectively. Plates 531, 541, and 551 are connected to the elongated support member 301 via flexible connectors 431, 441, and 451, respectively. Figure 7FIn the example shown, plate 541 and flexible connector 441 are connected to elongated support member 301 at arch 303 in eye contact device 126. Plates 511, 521, 531, 541, and 551 have anatomically adaptive toroidal protrusions 311, 321, 331, 341, and 351 extending from the posterior planar surfaces of plates 511, 521, 531, 541, and 551 adjacent to the sclera, respectively. The elongated support member, flexible connector, and protrusions provide surfaces for contacting the sclera. The remaining space includes an open space 250, which provides empty space between the features of eye contact device 126 to achieve independent and consistent feature adaptation and degrees of freedom. As illustrated, lower eyelid placement of the device also provides the opportunity to retain the generated tears for a longer duration within the eye space within the open space 250. Alternatively, the eye contact device can be placed under the upper eyelid (not shown). Protrusions 311, 321, 331, 341, and 351 extend from the rear surface of the plate, illustrating the surface interactions and relationships of protrusions with toroidal geometry. The protrusions have contact surfaces and can have different geometries besides toroidal or annular shapes. Protrusions can be convex shapes with contact surfaces. The contact surfaces of the protrusions can be convex.

[0295] exist Figures 7F to 7G In the device 126, plates 521, 551, 541, 531 and 511 are provided. Figure 7F The rear surface of the plate, configured to contact the sclera of the eye, is shown. Specifically, the eye-receiving device 126 has rear surfaces 322, 352, 342, 332, and 312, respectively. Figure 7G Plates 521, 551, 541, 531, and 511 (shown in the diagram) have at least one protrusion 321, 351, 341, 331, and 311 on their posterior surfaces. The protrusion has a convex contact surface for contacting the sclera of the eye and providing an offset space between the sclera and the posterior surface of the plate. The protrusion may define a periphery surrounding the offset space. The presence of the offset space between the sclera and the posterior surface of the plate provides further adaptation to the anatomy of the eye, thereby allowing tear formation between the sclera and the eye-connecting device. Figure 7F The protrusions in the example are annular, thus forming a complete ring, as an example of protrusions on the rear surface of the receiving device.

[0296] Figure 7G yes Figure 7F The horizontal cross-section of the through line 128 of the eye-connecting device 126 is shown. As viewed from the top of the eye-connecting device, an elongated support member 301 and an arch 303 are shown. Plates 521, 551, 541, 531, and 511 have protrusions 321, 351, 341, 331, and 311 extending from the rear surfaces 322, 352, 342, 332, and 312, respectively.

[0297] like Figure 7F and Figure 7G The toroidal features of the contact device shown provide a non-invasive contact device with minimal surface contact. Figure 7G In the middle, the posterior surfaces 322, 352, 342, 332 and 312 can be spaced apart from the surface of the sclera by protrusions, so that tears can collect in the offset space of the eye contact device 126, thereby providing an opportunity to increase the lubricity of tears.

[0298] The interaction between the protrusions on the plate and the eyeball can be described by referring to a ring, which is similar to a toroidal surface or band, and a sphere, which is similar to the eyeball. For simplicity, the ring and sphere are initially referred to as substitutes for the protrusions and the eyeball.

[0299] A ring with a diameter smaller than that of a sphere can be placed on the sphere regardless of the size of the sphere. The ring will find the correct circular surface on the sphere, regardless of the ring's orientation. Other geometric surfaces can also mate with each other on the circular surface, including, for example, convex and conical surfaces.

[0300] By applying these geometric principles to the eye-connecting device, protrusions such as rings or tori interact with the eyeball, allowing the protrusions to self-position on the eyeball regardless of its size or position on the device, thus providing adaptability to different eyeball sizes.

[0301] The presence of at least one protrusion with a convex contact surface (which contacts the sclera of the eye and provides offset space between the sclera and the posterior surface of the plate) reduces the surface area of ​​direct contact between the plate and the eyeball. That is, the convex contact surface of the protrusion contacts the sclera of the eyeball, and the surface area of ​​the convex contact surface is generally smaller than the surface area of ​​the posterior surface of the plate. The application of this surface interaction geometry principle provides an eye-connecting device with reduced static friction with adjacent surfaces.

[0302] Advantageously, eye-connecting devices that manage rapid salivation events and surface displacement during blinking reduce the impact on ocular anatomy and increase patient comfort. Adaptive eye-connecting devices that provide offset space, have a reduced contact surface area, and are capable of accumulating tear fluid within their geometry offer users a comfortable, highly lubricated wearable device that allows adaptation to different ocular anatomy in individuals and across populations.

[0303] Devices with protrusions that contact the eyeball beneath the eyelids of rapidly moving eyes possess a smooth, non-traumatic blended surface and minimal static friction near the sclera and eyelid anatomy, thus minimizing the traumatic device interface during eye saccadic movements. This can be achieved without suturing the device to the eye. As discussed more fully below, this type of device can be used, for example, to deliver materials to the eye.

[0304] Figure 7H Examples Figure 7G The image shows a right-side cross-sectional anatomical view of the eye-receiving device plate 511, where the plate interacts with the sclera 102 of the eyeball to form an offset space 089, allowing tears to flow within this space. Figure 7H As shown, the design of the example plate 511 allows the kinetic movement of the scleral surface to advantageously deviate from the plate 511 and come into contact with the tear fluid. The tear fluid provides lubrication, thereby increasing user comfort. The elongated support member, flexible connector, and protrusions contact the sclera while maintaining the offset space 089, thus retaining the tear fluid within the offset space. When the eye-connecting device is placed under the eyelid as illustrated, it retains additional tear fluid in the eye space for a longer duration, a result of the characteristics of the eye-connecting device and the surrounding open space 250 (see [reference]). Figure 7F When the eye-contact device is inserted under the eyelid, the active pharmaceutical ingredient can be delivered to the eye via tears.

[0305] Provides 8+ mm surface translation (Table 3, Figure 4A The 100-millisecond saccade duration of a 40-degree angular offset is a significant surface translation distance relative to the eyelid. Advantageously, the eye-receiving device, residing under the eyelid, has no adverse effect on the ocular anatomy during these events. The disclosed eye-receiving device is designed to generate a large volume of tears collected adjacent to the sclera to reduce or minimize surface-to-surface contact between the eye-receiving device and the sclera. Naturally generated tears can be held by the eye-receiving device or a portion thereof (including protrusions) due to its geometry. The eye-receiving device, when in place in the eye, can "float" during saccade translation due to the large volume of tears accelerated by surface translational mechanical movement, thus providing minimal resistance and reduced contact during these eye movement events. The natural adaptation of the eye-receiving device, including the plate and protrusions within the plate, to the differences in ocular anatomy enables the generation and retention of sufficient tears for this purpose.

[0306] exist Figure 7H middle, Figure 7GThe scleral surface 102 and plate 511 are shown in a sagittal plane section; additional material has been removed for clarity. The convex toroidal feature 311 of plate 511 is shown when it is fully adapted to and in contact with the scleral surface 102 via a convex geometry 311. The boundaries of the scleral surface 102, the protrusion 311, and the posterior surface 312 of plate 511 provide offset space 089 in which tears can form. Scleral movement in any direction will utilize its aspiration of tears, thereby providing the ability to displace plate 511 relative to the scleral contact, thus increasing the available tear volume and lubricity across the scleral surface contact area and reaching the protrusion within the device periphery.

[0307] Drug delivery.

[0308] The described eye-connecting devices can be adapted to the anatomy of the eye. Advantageously, these devices are comfortable within the ocular space, have reduced impact on the patient's vision, remain stable in placement and holding, and resist dynamic motion and visual forces.

[0309] Eye contact devices can be configured to hold and deliver substances to the user, such as drugs, pharmaceutical agents, or combinations of drugs, pharmaceutical agents, or drugs (collectively, "pharmaceutical agents" or "medicines"). The drug can be within the eye contact device itself, in a drug insertion component, or both. For example, the drug can be in a plate of the eye contact device. When the device is part of a delivery system, for example as part of an insertion scheme, the drug can also be applied to the device through a port. The drug can be in or across multiple plates, either singly or in multiple forms, or applied to the device through a delivery system port. For example, the plate may include recesses, and the drug can be in the recesses of the plate. Drug delivery can be achieved by transporting the drug to the ocular anatomy through various transport mechanisms. Advantageously, the eye contact device and transport mechanism are comfortable for the user and compatible with the ocular anatomy, and the eye contact device and transport mechanism are a combination that will deliver the drug to the ocular anatomy at a prescribed dose rate and total dose over a known time period. Given cost, it is further advantageous to avoid process loss of the drug.

[0310] Alternatively, a drug insert (also called an "insert") may be used with the eye-seeking device when the drug insert contains a substance such as a drug, pharmaceutical agent, or pharmaceutical active agent, wherein the drug insert serves as part of a transport mechanism or method for delivering the drug to the eye. The drug insert may be placed within the eye-seeking device, for example, in the plate of the eye-seeking device. The drug insert may be placed in an insert recess within the plate of the eye-seeking device.

[0311] For example, it can be done by... Figure 5AThe eye-viewing device 299 shown is combined with a drug insert to provide the user with an adaptive eye-viewing device for drug delivery, delivering therapeutic drugs or medicines to the user's eyes.

[0312] Figure 8A This is a flowchart illustrating an example of the manufacturing process of a clinical use device according to an exemplary embodiment.

[0313] Figure 8B This diagram uses Venn diagrams to illustrate the performance attribute contributions of eye-connecting devices and inserts (a must-know for drug delivery exams), as well as combinations of eye-connecting devices and inserts. Venn diagrams show individual and combined performance attributes. Drugs can be delivered via tears, either from the eye-connecting device or from an eye-connecting device with an insert. Tears are the transport mechanism that delivers drugs or medications to both the eye and the mucous membranes that absorb them. Drug delivery occurs across and through ocular anatomy structures very close to the eye-connecting device, and targeted therapy can be achieved using tears.

[0314] Figure 9A1 , Figure 9A2 and Figure 9B An example is an eye-contact device 598 that can be used to deliver substances, including medicines, to the eye. Figure 9A1 It is a front sectional view of the eye-receiving device 598 with a recess. Figure 9A2 yes Figure 9A1 The front view of the device, in which the insert is aligned to be inserted into the recess in the plate. Figure 9B yes Figure 9A2 The front view of the device, in which the insert is inserted into the plate.

[0315] It should be noted that the method of placing the insert in the receiving device or from, for example... Figure 9A1 , Figure 9A2 and Figure 9B The method of delivering medicine using a receiving device such as the one shown is not limited. For example, an insert can be mechanically placed in the receiving device. By way of example and not limitation, the insert can be mechanically placed in a recess in the plate of the receiving device. As another example, the insert can be produced in situ by polymerization. By way of example and not limitation, silicone can be polymerized with the medicine in the recess in the plate of the receiving device. For medicines from, for example... Figure 9A1 , Figure 9A2 and Figure 9B There are no limitations on the method of delivering drugs using the device shown in the diagram. For example, known drug delivery methods can be used. Drug delivery can be driven by controlling a flow diaphragm to generate single, multiple, or gradient drug delivery profiles and / or by charged, uncharged, or osmotic dose-driven processes.

[0316] The design focus of inserts can be to achieve dose-time targets for any therapeutic formulation, biologic, pharmaceutical, genetic interaction agent (“gene therapy”), and / or delivery method.

[0317] The illustrations of the configuration and arrangement of the receiving devices and inserts provide further details and are not intended to limit the receiving devices and inserts individually or in combination.

[0318] Figure 9A1 This is a front view of the eyepiece receiving device 598, in which a plate is cut in a horizontal plane to expose a recess. The eyepiece receiving device 598 includes plates 511, 531, 541, 551, and 521, each plate including an insertion recess 611, 631, 641, 651, and 621. For reference, Figure 9A1 The markings are on surfaces 312, 332, 342, 352, and 322. The receiving device 598 is located on... Figure 9A1 The middle part is shown as curved to illustrate its ability to adapt to the surface of the eyeball.

[0319] Figure 9A2 yes Figure 9A1 The front view of the receiving device 598 shows inserts 711, 731, 741, 751, and 721 aligned for insertion into recesses in the plate. A cross-sectional view of insert 731 is shown. Figure 9A2 In the middle, a material chamber with an opening or hole is exposed, which leads to the interior of the chamber. Figure 9A2 The insert 721 has a through hole to show a tubular or cylindrical insert design.

[0320] In order to assemble the receiving device 598 and the insert, the insert 711 is placed and fixed into the recess 611 in the plate 511; the insert 731 is placed and fixed into the recess 631 in the plate 531; the insert 741 is placed and fixed into the recess 641 in the plate 541; the insert 751 is placed and fixed into the recess 651 in the plate 551; and the insert 721 is placed and fixed into the recess 621 in the plate 521.

[0321] Figure 9A2 and Figure 9B The insert shown is configured to be assembled to the front side of the receiving device's plate.

[0322] Figure 9B yes Figure 9A2 A front view of the receiving device 598, wherein the insert is inserted into a recess in the plate.

[0323] Figure 10A and Figure 10B Example of a receiving device 598. Figure 10A This is a front view of the receiving device 589, in which the plate is cut on a horizontal plane to expose a recess in the plate. Figure 10A This is a front view showing the eyepiece device 589 and the different inserts aligned to be inserted into the recesses in the respective plates. Figure 10A The inserts in the plate 511 have sealing diaphragms. Insert 712 has a sealing diaphragm 713, insert 722 has a sealing diaphragm 723, insert 732 has a sealing diaphragm 733, insert 742 has a sealing diaphragm 743, and insert 752 has a sealing diaphragm 753. As an example, insert 712 with sealing diaphragm 713 is placed in recess 612, and diaphragm 713 is sealed to the rear surface 312 of plate 511. Figure 9A2 The insert 721 shown also has an eyelid drug release opening 70, which, when combined with... Figure 10A When the illustrated receiving device 589 and the plate 541 with the hole 072 are used together, a bidirectional conveying system is provided. The insert 721 is an example of a cored insert with a hole through which it passes.

[0324] Figure 10B yes Figure 10A A front view of the receiving device 589, in which the insert is inserted into the plate.

[0325] Treatment drugs can be delivered together or sequentially using single or multiple inserts and drug delivery technologies (see [link]). Figure 9A2 Insert 741).

[0326] The insert and sealing diaphragm can be made using any volumetric shape suitable for the design and function of the insert and sealing diaphragm, which will provide volume, including but not limited to: squares, rectangles, triangles, polygons, circles, ellipses, spheres, spline surfaces, films, and combinations thereof (as appropriate). Such geometry will then create open spaces within which the geometry of the insert remains and is held.

[0327] The composition and design of a sealing diaphragm, which can be applied alone or in combination with an insert, can be any suitable pharmaceutical delivery material and / or system, such as: porous materials, foams, meshes, slits, orifices, woven, nonwoven, permeable membranes, polymer membranes, layered, complexes, laminates, metallic structures, polar and nonpolar properties. All useful examples of controlled release barriers represent only a few of the many possibilities of composition and construction.

[0328] Examples illustrate eye-access devices for positioning and holding inserts within the anatomy of the eye to provide comfort in an adaptive ophthalmic drug delivery system, which may include inserts to provide therapeutic clinical effects. Examples illustrate the depth, breadth, and versatility of eye-access devices disclosed across a variety of possible drug delivery schemes.

[0329] Figure 11AThe front view of the receiving device 298 shows the drug delivery system, and Figure 11B yes Figure 11A A bottom view of the system. The eye-connecting device 298 includes an elongated support member 301 having an arch 303, which can be inserted under the eyelid (at the eyelid, the elongated support member can self-position to adapt to the anatomical structure) and can rotate about its horizontal axis. When the eye-connecting device is in place, the elongated support member 301 extends toward each corner of the eye, and plates 511 and 521 are connected at each end of the elongated support member 301 by flexible connectors 411, 421. Between plates 511 and 521, plates 531, 551 adapted to the eye anatomy are connected to the elongated support member 301 by flexible connectors 431 and 451. An open space 250 (e.g., in...) Figure 11B (As shown in the diagram) Empty spaces are provided between the features of the eye-connecting device 298, thereby providing unoccupied volume for tear retention within the constraints of the eye-connecting device and for the independent and consistent adaptation of the features of the eye-connecting device. Plates 511, 531, 551 and 521, flexible connectors 411, 431, 451 and 421, and an elongated support member 301 with an arch 303 are individually and consistently adapted to the anatomy of the eye and provide an eye-connecting device that can deliver drugs or medicines to the eye under the eyelids.

[0330] The recesses within plates 511, 531, 551, and 521 allow for the placement and retention of medications or drugs to provide the desired therapeutic effect.

[0331] Figure 12A The device 597 is depicted, exemplified by an elongated support member 301 with an arch 303, which is shown connected to plates 511, 531, 551 and 521, which are divided in a horizontal plane to expose recesses 611, 631, 651 and 621 in the plates, respectively.

[0332] The recess is configured to hold the insert within the plate of the receiving device. The rate of drug delivery over time can be controlled by adjusting the small-diameter lip opening (in which the insert is pressed), thus providing a mechanical holding system for erosive or non-erosive inserts.

[0333] Figure 12BAn example of a connector 587 is shown. In addition to the diaphragm seal as previously described, the connector 587 includes features for securing the insert such that the insert is designed to mate with recesses 622, 652, 632, and 612. The insert, placed within the recess, is mechanically held by retaining features illustrated by 325, 355, 335, and 315, respectively. Mechanical holding is achieved by a retaining lip, as shown. There is no directional limitation regarding the addition of this feature; it may also be included in other designs. Figure 12A In the receiving device.

[0334] An elongated support member 301 with an arch 303 is shown in cross-sectional view connected to plates 521, 551, 531, and 511, which include recesses 622, 652, 632, and 612, wherein the rear surfaces 322, 352, 332, and 312 can be used for additionally easy sealing of the diaphragm element. Plates 551 and 531 are illustrated to include large-volume recesses 632 and 652, respectively, and optional diaphragm planar sealing features 332 and 352.

[0335] The receiving device 587 can hold the insert. Features 315, 325, 335 and 355 can be configured to control the drug delivery rate by controlling the orifice size, while features 612, 622, 632 and 652 provide opportunities for the delivery of large quantities of drug, which can be sustained for a longer period of time due to the design and composition of the insert itself.

[0336] Figure 13A , Figure 13B and Figure 13C Another example of a receiving device is shown, namely receiving device 596.

[0337] like Figure 13A As illustrated, the eye-accessing device 596 can be inserted under the eyelid and adapted to the differences in eye anatomy. When the eye-accessing device is in place, an elongated support member 301 extends toward each corner of the eye, and plates 511 and 521 are connected at each end of the elongated support member 301 via flexible connectors 411 and 421. Between plates 511 and 521, plates 531 and 551 adapted to the eye anatomy are connected to the elongated support member 301 via flexible connectors 431 and 451. Plates 511, 531, 551, and 521, flexible connectors 411, 431, 451, and 421, and the elongated support member 30 with an arch 303 are individually and uniformly adapted to the eye anatomy and provide an eye-accessing device that can deliver drugs or medicines to the eye under the eyelid.

[0338] Figure 13B This is an example of a top view of the receiving device 596. Figure 13BIn the middle, plate 531 shows a recess 633 and a sealing diaphragm 333. Plate 551 shows a recess 653 and a sealing diaphragm 353.

[0339] Figure 13C This is an example of a front view of the receiving device 596, in which plates 531 and 551 are cut open to expose the interiors of recesses 633 and 653.

[0340] Figure 14A , Figure 14B and Figure 14C A receiving device 595 is illustrated as another example of a receiving device. The receiving device 595 has a plate with a larger recess.

[0341] Figure 14A This is a front view of the receiving device 595. (Example) Figure 14A As illustrated, the eye-contact device 595 includes an elongated support member 301 with an arch 303 and plates 5102 and 5202, which can be placed adjacent to the corner of the eye and are connected to the elongated support member 301 via flexible connectors 4112 and 4212, respectively. Plate 5102 has a recess 630 and plate 5202 has a recess 650. Recesses 630 and 650 can receive substances such as medicines to be delivered to the eye.

[0342] Figure 14B yes Figure 14A The figure shows a horizontal cross-section of the through line 139 of the receiving device 595. The figure also shows a cross-section of a plate 5102 having a recess 630, a protrusion 320, and a rear surface 350, and a cross-section of a plate 5202 having a recess 650, a protrusion 310, and a rear surface 330.

[0343] Figure 14C yes Figure 14A The front view of the receiving device 595 shows recesses 630 and 650 in its cross-section on a vertical plane.

[0344] Figure 15A , Figure 15B and Figure 15C A receiving device 594 is shown as another example of a receiving device. The receiving device 594 has plates 5103 and 5203.

[0345] The eye-connecting device 594 has a reduced conjunctival sac width and vertical height. Therefore, the eye-connecting device 594 is advantageous for users with an ocular anatomy that has a smaller conjunctival sac volume (e.g., users with a narrow palpebral fissure width and a reduced fornix depth).

[0346] like Figure 15AAs shown, the front side of the receiving device 594 includes a segmented circular surface the width of the surrounding plates 5103 and 5203 (see Figure 1). Figure 22B The elongated support member 301 extends toward each corner of the eye when inside the eye. Flexible connectors 471 and 481 are configured to be positioned further away from the corners of the eye when inserted into the user's eye, while plates 5103 and 5203 adjacent to the corners of the eye are configured to be more centrally located within the conjunctival sac's ocular anatomy. As a result, flexible connectors 471 and 481 extend beyond the plates, thereby positioning the plates such that when the eye-connecting device 594 is inside the eye, the plates face the vertical midline of the eye. Consequently, the eye-connecting device 594 has a reduced width in the area of ​​the plates to be inserted into the conjunctival sac, and the eye-connecting device 594 has a wider, elongated support member.

[0347] Flexible connectors 471 and 481 are vertically bent from the elongated support member 301, thereby hinged around local origin pivots 472 and 482 to be connected to plates 5103 and 5203 respectively in a spring-ring manner. The eyepiece device 594 is adjustable for anatomical forces while incorporating spring-ring features, and the eyepiece device maintains a generally controlled and predictable shape outside the eye space. Users may prefer to handle the insertion and removal of the device with a predictable shape, providing a feature similar to contact lenses. Softer, more flexible, adaptable material compositions can also be used without sacrificing the user's desired ease of operation.

[0348] Figure 15B Examples are shown as follows Figure 15A The bottom view of the receiving device 594 shown.

[0349] Figure 15C A partial cross-sectional bottom view of plate 5103 of the receiving device 594 is shown. Plate 5103 appears... Figure 15C In the middle, there are optional recesses 620 and protrusions 3103, the protrusions 3103 being toroidal and segmented (see...). Figure 22B The recess 620 opens toward the posterior surface 3303 of the plate 5103 and is positioned such that when it is in the eye, the recess is adjacent to the sclera and offset from the surface of the sclera by the protrusion 3103.

[0350] Figure 16A and Figure 16B An example of a connection device 593 is shown. In the connection device 593, an elongated support member 301 and a flexible connector are bent around points 472 and 482 to connect with plates 5114 and 5214, and these plates are connected to plates 531 and 551, respectively.

[0351] Figure 16AThis is a front view of the receiving device 593. The receiving device 593 contains four plates 5114, 531, 551, and 5214. Plates 531 and 551 have recesses 631 and 651, respectively. Plate 5114 is connected to the elongated support member 301 via a flexible connector 471 and to plate 531 via a plate connector 432. Similarly, plate 5214 is connected to the elongated support member 301 via a flexible connector 481 and to plate 551 via a plate connector 452.

[0352] Flexible connectors 471 and 481 are connected to elongated support members 301 and bend around points 472 and 482 to connect to plates 5114 and 5214. The flexible connectors are configured to be positioned further away from the corner of the eye when inserted into the user's eye, while plates 531 and 551 are configured to be more central within the eye's anatomy.

[0353] As an alternative Figure 16A The connections of boards 551, 5214, 5114, and 531 can be made as follows: Figure 16A This is achieved by the support members 452 / 481 / 301 / 471 / 432 that are embedded in or pass through the plate.

[0354] Figure 16B yes Figure 16A The top view of the connector 593 shown is rotated 180° to show the connection between plate 5114 and plate 531 via connector 432, and the connection between plate 5214 and plate 551 via connector 452. Figure 16B As shown, connectors 432 and 452 can be offset from the rear surfaces 3114, 3214, 331 and 351, thereby reducing constraints on the movement of board connectors 432 and 452 that may be caused by the surface of the eye anatomy.

[0355] Figure 17A and Figure 17B Example of a receiving device 592. Figure 17A A front view of the receiving device 592 is shown, and Figure 17B A rear view of the receiving device 592 is shown as an example. The receiving device 592 is larger than... Figure 12A and Figure 12B The connecting devices 597 and 587 shown are more compact. In the connecting device 592, each plate is connected to the elongated support member 301 without an intermediary plate.

[0356] Figure 17BThe flexible connectors 471 and 481 are shown to also bend around points 472 and 482 to form an outer angle 130. The outer angle 130 is an obtuse angle. Further flexibility in providing a device suitable for a particular user can be achieved by providing a device with obtuse angles, acute angles, or a combination of obtuse and acute angles. Additional options are also available in the angle formed at the connection between each plate of the connector disclosed herein and the elongated support member in each of the disclosed connectors. For example, in Figure 11A In the design, the angle formed between the flexible connector 431 and the elongated support member 301 on the left side of the flexible connector is an obtuse angle. In a specific device, the connection angles between the plate and the flexible connector with the elongated support member can be the same or different.

[0357] Figure 18A , Figure 18B and Figure 18C Example of a receiving device 591. Figure 18A This is a front view of the eyelid receptacle. The eyelid receptacle 591 can be oriented with the rear or front of the plate facing the sclera. Protrusions on the plate of the eyelid receptacle 591 engage and adapt to the sclera and eyelid, having curved surfaces regardless of curvature, orientation, or size. The flexibility in the placement orientation of the eyelid receptacle 591 simplifies user guidance and training.

[0358] Figure 18B yes Figure 18A A top view of the receiving device 591. From Figure 18A and Figure 18B It can be understood that each feature of the eye-connecting device 592 is freely translatable horizontally and vertically, and rotates upon insertion to conform to the anatomy of the eye, and each plate and protrusion is also freely oriented to adapt, thus providing a device that can be inserted in either direction.

[0359] Figure 18C yes Figure 18A A top view of the eye-connecting device 591, wherein the top portion of the plate is cut off. The device is shown as twisted around arch 303 to deflect the plate off the centerline of the device, wherein plates 511 and 531 are twisted relative to plates 551 and 521 to simultaneously illustrate the front and rear portions of the plates. Plates 511, 531, 551, and 521 have protrusions 311, 331, 351, and 321 and “rear surfaces” 312, 332, 352, and 322. Plates 531 and 551 have recesses 631 and 651, respectively. The term “rear surface” is in quotation marks because 312, 332, 352, and 322 appear on either side of their respective plates to emphasize that the eye-connecting device 591 can be inserted into the eye in either direction.

[0360] Figures 19A to 19HAn isolated view illustrating the eye-viewing device 800 and its features is shown. The eye-viewing device 800 has a large volume and can be inserted under the eyelid.

[0361] Figure 19A , Figure 19B and Figure 19C These are the front view, top view, and rear view of the viewing device 800. The consecutive figures illustrate the device while maintaining its left-right orientation, rotating about the supporting member toward the observer in 90° increments.

[0362] As in Figure 19A and Figure 19C As can be seen, the slender support member 801 is segmented from the central arch, having a variable cross-section. Considering the distribution of material flow, the design of the receiving device 800 is advantageous for thermoplastic injection molding processes. From Figures 19A to 19C As can be understood, the connector 800 incorporates and adapts features more fully described with reference to other connectors exemplified herein. The connector 800 allows for predictable adjustment of features and connectivity to accommodate a wide range of polymer compositions, each with its own process and thermo-dimensional properties.

[0363] The cavities in the tablet have large-volume cylindrical recesses for the pharmaceutical product or inserts for containing the product, compatible with well-known tablet manufacturing techniques, and assembled via snap-fit ​​mechanical components. Other sealing diaphragms, as illustrated above, can be used. The insert dimensions provide cavities with large volumes, thus advantageously providing a high drug-to-carrier weight ratio.

[0364] like Figure 19C As shown, plates 812, 822, 832, 842, 852, and 862 are generally arranged across the corner of the eye. Protrusions 813, 823, 833, 843, 853, and 863 rest on plates 812, 822, 832, 842, 852, and 862, respectively, and have convex contact surfaces for contacting the sclera of the eye and providing offset space between the sclera and the posterior surface of the plates.

[0365] Flexible connectors 810, 820, 830, 840, 850, and 860 connect the plate to the elongated support member 801. Figure 19A and Figure 19C The plates 812, 822, 832, 842, 852 and 862, which are flexibly connected along the elongated support member 801, also include features 811, 821, 831, 841, 851 and 861, which are materials of the front side of the plates that extend toward and contact the eyelids.

[0366] Figure 19D , Figure 19E , Figure 19F and Figure 19H They are respectively along Figure 19A The cross-sectional views of lines AA, BB, CC and DD of the device.

[0367] like Figure 19D As illustrated, plate 811 includes a rear surface 812 and a protrusion 813 having a convex contact surface for contacting the sclera of the eye and providing offset space between the rear surface and the sclera.

[0368] Figure 19E An example of a cut plate 831 is shown, illustrating the rear surface 832 and protrusions 833, as well as a flexible connector 830, wherein there is an offset space between the sclera and the rear surface 832 of the plate 831.

[0369] Figure 19F An example is shown, plate 851 having a recess 871 and retaining elements 875, 876, and 877 capable of holding an insert. Recess 871 is an example of a recess that can accept a cylindrical insert, which may, for example, have a radius 875 and a width (not shown), to be pushed by the retaining lip 876 and thus remain and be secured within plate 851. Figure 19F and Figure 19H Seen in the cross-sectional view and Figure 19A As shown in the front view, maintaining the distance between the lip edges 876 provides an opening to the recess 871.

[0370] Figure 19G This is an isometric view of a portion of the receiving device 800 in Figure 19, wherein the plate is cut to expose recesses in the plate. Figure 19G Alternative pits are illustrated, demonstrating that optional eyelids and optional sclera can control the drug delivery port. Figure 19G Other variations in the arrangement of the recesses in the receiving device 800 are shown. Figure 19G Visible in the image are the cross-sectional cuts of slender support members 801, plates 811, 831, and plate 851, with plate 851 having a modified drug insertion recess 871. The recess can be designed to deliver drugs in more than one direction; for example, the plate provides drug delivery in two directions. For instance, Figure 19G The recess 871 shown in the figure has Figure 19F The feature shown includes the addition of an aperture 878 through the plate 851, thereby providing an auxiliary delivery path for the direct delivery of medication to the sclera via the aperture 878.

[0371] Figure 19HA plate 861 with a recess 881 and a lateral width 889 is shown. A cylindrical or rod-shaped insert with a large volume can be inserted laterally to the plate 861. The cylindrical or rod-shaped insert can be configured to carry a larger volume of medicine or other substance to be delivered to the eye. The recess can have any geometric arrangement that secures the insert and exposes at least a portion of the insert's surface to the tear. The geometry of the eye-contact device can be used to retain the insert, particularly within the recess of the eye-contact device. By way of example and not limitation, the insert can be... Figure 19F neutralization Figure 19G Feature 876 shown is held within the recess of the receiving device 800.

[0372] Figure 19I It can be inserted into a receiving device (including...) Figures 19A to 19H An isometric view of a medicine insert or an example of an insert in a receiving device. Figure 19I The insert is rod-shaped, which is an example, not a limitation, of the shape or size of the insert to be inserted into the connector 800 or other connector.

[0373] Figures 20A to 20G An example of the orientation of a recess for a pharmaceutical insert is shown, with the recess shown along a generally transverse (horizontal) plane to illustrate its characteristics. This illustration is not a limiting or restrictive "orientation" for any pharmaceutical insert recess. As a non-exclusive alternative example, it may be compatible with manufacturing processes used to align the recess with or perpendicular to flexible connectors.

[0374] Figure 20A This is a front view of the receiving device 1008. (Except for...) Figure 20A In addition to the previously described features of the receiving device, which can also be seen in the diagram, the receiving device 1008 includes support curves 1301 and 1304 that are separated from each other. It should be understood that the recesses 1631 and 1651 in plates 1531 and 1551 may be transverse as shown, or in another orientation.

[0375] A horizontal surface 1302 spans the interior of arch 1303, thus providing an anchor around which other features can exercise their degrees of freedom. The horizontal surface 1302 also provides attachment points for manufacturing accessories. See also Figure 6B This is in contrast to the discussion above regarding the lower side 302 of arch 303.

[0376] Figure 20B It is along Figure 20A The cross-sectional view of the line BB of the receiving device, and Figure 20C It is along Figure 20A A cross-sectional view of line AA of the receiving device. The receiving device 1008 has, for example, in connection with... Figure 20CPlates 1511, 1531, 1551, and 1521 are further described in the discussion. Figure 20B The protrusions 1311 and 1331 shown are similar to, for example, those in the... Figures 21A to 21L The features further shown and described in the discussion. The recess 1631 is similar to, for example, in... Figures 19A to 19H The cavity is further shown and described in the text.

[0377] Figure 20C A cross-section of plate 1531 is shown, with the rear surface 1332 facing to the right. (See diagram) Figure 20C As can be seen, the recess 1631 in plate 1531 has an elliptical peripheral cross-section of surface 1871. The recess 1631 can securely capture the insert and provide sufficient "lateral clearance" and "end clearance" to allow tear fluid to reach the insert surface within the recess. Figure 20C The method shown in 1876 for maintaining the lip line is not required. Figure 20B The continuous features shown across its span 1889; specifically, the retaining lip 1876 can be one or more “finger-like” geometries with material relief between them, so that when the insert is held within the eye contact device 1008, tears enter the compartment 1631 and contact the insert surface 1900. Figure 20C The recess 1631 is shown in dashed lines. The insert 1900 fits into the recess 1631, which has an elliptical cross-section. Figure 20B An example insert length compatible with the span 1889 of recess 1631 is shown.

[0378] The recesses in the plate can have the above reference Figure 10A The orifice or hole 072 on plate 541 describes the tear delivery capability in two or more different directions. Similarly, Figure 20A , Figure 20B and Figure 20C The plate of the eye-receiving device 1008 shown may include holes, openings, or slits to allow medicine to exit from the scleral side of the plate into a recess in the plate, thereby providing a tear path from the scleral side of the plate into the recess.

[0379] It should also be understood that the plate may include one or more snap-fit ​​features that can mechanically retain the insert.

[0380] It should also be understood that the recess 1631 can be any useful shape that can capture and retain the insert.

[0381] Figure 20D yes Figure 20A The front view of the receiving device is simplified so that no recesses appear in the plate.

[0382] Figure 20E Is it like this? Figure 20D The eye-viewing device shown is illustrated with shading to indicate an open space 250 within the periphery of the eye-viewing device and defined by the eyelids.

[0383] Figure 20F yes Figure 20E The open space 250 has the eye-viewing device removed. When the eye-viewing device 1008 is inserted into the eye, tears can fill the open space 250.

[0384] Figure 20G yes Figure 20F A front view of the open space 250 at a 45-degree angle. When in the eye, the eyelids droop over the device to define the boundary of the open space 250. See, for example... Figure 7A , Figure 7B and Figure 7C .

[0385] In the receiving device, each plate with a recess can contain inserts with different pharmaceutical active agents. For example, two recesses with two different pharmaceutical active agents can exist in a single device. A recess can have inserts containing more than one active agent.

[0386] Human eye compatibility and comfort.

[0387] Advantageously, the eye-viewing device is compatible with the anatomy of the human eye, and users find it comfortable. The following list provides features that can increase the compatibility and comfort of the eye-viewing device. This list is not intended to limit the eye-viewing devices disclosed herein.

[0388] Location below the eyelid.

[0389] The anchoring and stabilizing geometry near the corner of the eye maintains the position and centering of the eyelid.

[0390] Minimal contact with the sclera is required to reduce the impact from eye sacral movements.

[0391] Enhance tear volume retention and tear retention time for user comfort and continuous delivery of medication to the eye's anatomy.

[0392] Optically high quality polished surfaces are used to increase surface area, enhance tear production, and reduce eye movement friction.

[0393] Self-adaptation to a range of scleral and eyelid anatomy and local anatomical differences.

[0394] Overall flexibility in the size, technology, composition, and placement of treatment inserts.

[0395] Minimal eye-occupancy configuration compatible with the smallest eye physiology.

[0396] Extensive anatomical conjunctival sac width: fit, configure, and design capabilities.

[0397] The material composition is designed to be hydrophilic and eye-friendly for patient comfort.

[0398] Figures 21A to 21L Examples of plates and protrusions are shown, which may be different configurations of the receiving device or used in the receiving device.

[0399] Figure 21A This is a perspective view of an example plate 911 including a rear surface 912, the rear surface 912 having an annular protrusion 913, in this example, the annular protrusion 913 forming a complete ring.

[0400] Figure 21B This is a perspective view of an example plate 921 including a rear surface 922, the rear surface 922 including a protrusion 923, in this example, the protrusion 923 being an open segment of a toroidal surface.

[0401] Figure 21C This is a perspective view of an example plate 931 including a rear surface 932, the rear surface 932 including a single dome-shaped protrusion 933, the protrusion 933 being disposed eccentrically relative to the center of the plate 932. Figure 21D The image shows a magnified view of the small, centrifugal protrusion 933. Figure 21C The example plate 931 can be formed with a dome-shaped curved surface 934, which extends in a direction opposite to that of the protrusion 923. For example, in Figure 21A , Figure 21B and Figure 21F As can be seen, plates 911, 921 and 941 similarly form dome-shaped curved surfaces.

[0402] like Figure 21E As illustrated by plate 941, the plate may include multiple protrusions 943. For example... Figure 21E As shown, multiple protrusions 943 may be arranged at the periphery of the rear surface 942. The front surface of the plate 941 forms a dome-shaped curved surface 944 on the opposite side of the plate relative to the rear surface 942. Figure 21F Further examples are shown in the text. Figure 21F yes Figure 21E (Cross-sectional view of plate 941), each protrusion 943 has a contact surface.

[0403] Figure 21G It is a perspective view of an example plate 951 including a rear surface 952, the rear surface 952 having a protrusion 953, the protrusion 953 having a contact surface 955.

[0404] Figure 21H It is along Figure 21G Line 128 is cut from the middle. Figure 21G The left-side cross-sectional view of plate 951 and the sectional view of sclera 102 show the contact between the contact surface 955 of protrusion 953 and sclera 102. Plate 951 includes a front surface 954 on the opposite side of the plate relative to the rear surface 952. When plate 951 is placed under the eyelid, contact surface 955 contacts sclera 102 and front surface 954 contacts eyelid (not shown).

[0405] Figure 21I It is a perspective view of an example plate 961 including a rear surface 962, the rear surface 962 having a protrusion 963, the protrusion 963 having a contact surface 965.

[0406] Figure 21J It is along Figure 21I Line 128 is cut from the middle. Figure 21I The left-side cross-sectional view of plate 961 and the sectional view of sclera 102 show the contact between the contact surface 965 of protrusion 963 and sclera 102. The plate includes a front surface 964 on the opposite side of the plate relative to the rear surface 962. When plate 961 is placed under the eyelid, contact surface 965 contacts sclera 102 and front surface 964 contacts eyelid (not shown).

[0407] Figure 21K It is a perspective view of an example plate 971 including a rear surface 972, the rear surface 972 having a protrusion 973, the protrusion 973 having a contact surface 975, the contact surface 975 being a combination of a curved surface 975A, a generally planar surface 975B and a curved surface 975C.

[0408] Figure 21L It is along Figure 21K Line 128 is cut from the middle. Figure 21K The left cross-sectional view of plate 971 and the sectional view of sclera 102. Figure 21K The contact between contact surface 975 and sclera 102 is shown. It should be understood that at any given time, any one of contact surfaces 975A, 975B, and 975C can be in contact with sclera 102.

[0409] Figure 21L Also shown is a front surface 974 on the opposite side of the plate from the rear surface 972, the front surface 974 having a protrusion 976, the protrusion 976 having a contact surface 977, the contact surface 977 being a combination of 977A, 977B, and 978C. (As shown) Figure 21L As shown, protrusion 977 contacts eyelid 118 having eyelid flap 018. It should be understood that, although in Figure 21K or Figure 21L Not shown, but plate 971 can be placed under eyelid 118 with its anterior surface 974 facing sclera 102, in which case the contact surface 977 of protrusion 976 will contact sclera 102. It should also be understood that once plate 971 is placed under eyelid 118 with its posterior surface 972 facing sclera 102, it can be rotated or moved around so that its anterior surface 974 faces sclera 102. Therefore, plate 971 with protrusions 973 and 976 can be placed under eyelid with either its posterior or anterior surface facing sclera 102. This is the case whether plate 971 is placed under eyelid alone as an eye-connecting device or as part of an eye-connecting device with other features such as an elongated support member; the eye-connecting device (of which plate 971 is part) is placed under eyelid.

[0410] The diagrams and descriptions of the plates and protrusions are provided as examples and not as limitations.

[0411] Figures 21A to 21L Examples of plates with different shapes having protrusions arranged as shown are given. The shape of the plate and the arrangement of the protrusions are not limiting, and other shapes and arrangements are contemplated. These are provided as examples, not as limitations. Figures 22A to 22E Other plate shapes and protrusion arrangements are illustrated.

[0412] Figure 22A This is a front view of an adaptable, non-directional eye-catching device 1000 without a central "arch," according to another example of an eye-catching device. The eye-catching device 1000 includes two combined elements 1011 and 1021 connected to an elongated support member 1001. (As shown...) Figure 22A As demonstrated by the eye-connecting device in this study, the arch shown in other eye-connecting devices is unnecessary. The eye-connecting device 1000 without an arch can be inserted under the eyelid and deliver medication to the eye. Figure 22A The connection device shown illustrates an angular rotation extension of an elongated support member 1001 connected to a plate 1021 at an angle 132 greater than 180 degrees, illustrating further flexibility of the connection device disclosed herein.

[0413] Figures 22B to 22E Examples of convex scleral interaction features (e.g., protrusions) that can be used with embodiments of the present invention are illustrated. Protrusions provide a convex contact surface for contacting the sclera of the eye.

[0414] Figure 22B Examples Figure 22AThe plate 1011 includes a rear surface 1030 having protrusions 1010 and 1013, the protrusions 1010 and 1013 having convex contact surfaces formed by two toroidal sections.

[0415] Figure 22C Example plate 1021 is shown, which includes a rear surface 1030 having protrusions 1013, 1023, the protrusions 1013, 1023 having convex contact surfaces formed by two domes 1023 and annular segments 1013.

[0416] Figure 22D Example plate 1031 is shown. Plate 1021 includes a rear surface 1030 having protrusions 1023, 1033, 1043, the protrusions 1023, 1033, 1043 having convex contact surfaces formed by a combination of dome 1023 and toroidal swept sections 1033, 1043.

[0417] Figure 22E yes Figure 22D The cross-section of plate 1031 is shown. The cross-section of dome-shaped protrusion 1023 is also shown. Figure 22E The front surface shown (which is on the side of the plate opposite to the rear surface) can follow Figure 5B The planar curve 300 is shown in the figure. The eyelid can hang on the surface of the plate that is shaped to follow the planar curve 300.

[0418] Figure 23A The front view of the eye-receiving device 1201, which is placed under the eyelid, is illustrated. Figure 23B The features of the rear view are illustrated, and the viewing device 1201 is provided to illustrate various aspects of the disclosed viewing device. For example... Figure 23A As shown, the eye-accessing device 1201 includes: an elongated support member 3015 of flexible material configured to be positioned under the eyelid of an eye (not shown); and plates 5105, 5205 connected close to each end of the support member 3015 and substantially coplanar with the support member. Figure 23B As shown, each plate 5105, 5205 includes a rear surface 3125, 3225, the rear surface having at least one protrusion 3115, 3215 having a convex contact surface to contact the sclera of the eye and provide offset space between the sclera and the rear surface 3125, 3225 of the plate 5105, 5205.

[0419] Figure 23C This is a front view of the eye-viewing device 1203 to be placed under the eyelid. Figure 23D This is a rear view; the viewing device 1203 is provided to illustrate various aspects of the disclosed viewing device. For example... Figure 23CAs shown, the eye-accessing device 1203 includes: an elongated support member 3017 of flexible material configured to be positioned under the eyelid of the eye (not shown); and plates 5107, 5207 connected close to each end of the elongated support member 3017 and substantially coplanar with the support member. Figure 23D As shown, each plate 5107, 5207 includes a rear surface 3127, 3227, the rear surface having at least one protrusion 3117, 3217 having a convex contact surface to contact the sclera of the eye and provide offset space between the sclera and the rear surface 3127, 3227 of the plate 5107, 5207, wherein at least one protrusion 3117, 3217 is annular.

[0420] Figure 23E This is a front view of the eye-viewing device 1202 placed under the eyelid. Figure 23F This is its rear view; the receiving device 1202 is provided as another example of a receiving device. (See also...) Figure 23E As shown, the eye-receiving device 1202 includes: an elongated support member 3016 of flexible material configured to be positioned under the eyelid; and at least one plate 5106 connected to the support member 3016. Figure 23F As shown, the plate 5106 includes a rear surface 3126 having at least one protrusion 3116 having a convex contact surface to contact the sclera of the eye and provide offset space between the sclera and the rear surface 3126 of the plate 5106.

[0421] Figure 23G The front view of the receiving device is 1204. Figure 23H This is its rear view. Figure 23I yes Figure 23H The cross-section is illustrated by the convex protrusion surface 9348 of the plate (also shown in the image). Figure 23G (See in the image). The protrusion 9348 is relative to the above. Figure 21F Other examples of convex front surfaces discussed in the examples ( Figure 21E (Cross-sectional view). As discussed, Figure 21F An example of a front surface of a plate is provided, the plate example having a rear surface 942, a protrusion 943 extending from the rear surface 942 and a convex front surface 944. Figure 23I yes Figure 23H The image shows a cross-sectional view along AA of plate 5108 of the receiving device 1204, which is provided to illustrate other examples of the disclosed receiving devices.

[0422] like Figure 23GAs shown, the eye-viewing device 1204 includes an eye-viewing device for placement under the eyelid, comprising: an elongated support member 3108 of flexible material configured to be positioned under the eyelid; and at least one plate 5108 connected to the support member 3108. Figure 23H As shown, plate 5108 includes a rear surface 3128 having at least one protrusion 3118. The protrusion 3118 has a convex contact surface to contact the sclera of the eye and provides offset space between the sclera and the rear surface 3128 of plate 5108. The protrusion 3118 of the eye-viewing device 1204 is annular. As in Figure 23G As can be seen, the protrusion 3118 has a surface 9348 on the front of the plate 5108, and the surface 9348 can contact the eyelid when the eye-viewing device 1204 is in the eye.

[0423] Further reference Figure 23G and Figure 23I , Figure 23H of Figure 23H The cross-sectional view of the posterior convex annular scleral convex contact surface 3118 includes the anterior convex eyelid contact surface 9348 (which can also be in...). Figure 23G As seen in the image, the contact surface is a ring-shaped protrusion extending toward the front side of 1024 (where the eyelid is located).

[0424] Plate 5108 is not constrained by the periphery of the protrusion geometry of 3118 and 9348, and the posterior surface 3128 of plate 5108 does not completely block the posterior protrusion geometry feature 3118 and the anterior protrusion geometry feature 9348, thus resulting in a material-free region, also referred to herein as an open space, defined anteriorly and posteriorly by the sclera and eyelid respectively, remaining within the maximum periphery of the combined plate 5108 and the posteriorly facing protrusion geometry 3118. The posterior surface 3128 of plate 5108 and the inner surface of the eyelid near the material-free region can both be defined as the scleral surface and the distal surface of the protrusion 3118. Therefore, the tear volume of this device is considerably larger than that of other sublime eyelid devices in the art.

[0425] Surface 3128 is at a different scleral offset height than the eyelid defined by protrusion 3118. The eyelid is the surface furthest from the sclera.

[0426] Figure 24A , Figure 24B and Figure 24C Example of a receiving device 3592. Figure 24A This is a front view of the receiving device 3592. Figure 24B This is a rear view of the receiving device 3592, and Figure 24C It is along Figure 24A A cross-sectional view of the line AA of the receiving device.

[0427] In order to facilitate the orientation of the eye-viewing device 3592 in the eye with the rear or front surface of the plate facing the sclera, plates 3511 and 3521 have protrusions 3311 on both the rear and front surfaces, and plates 3531 and 3551 have protrusions 3331 on both the rear and front surfaces.

[0428] As in Figure 24A and Figure 24C As can be seen, plates 3531 and 3551 have recesses 3631 and 3651 that are open on both the front and rear surfaces. The eyelet device 3592 illustrates the possibility that the eyelet device can be made with polygonal (such as hexagonal) holes or openings leading to the recesses of the plates, and the openings can have different sizes. (As shown in...) Figure 24C As can be seen, the insert can be held in the plate by maintaining the lip edge 3332.

[0429] Figure 24D It can be inserted into a receiving device (including Figures 24A to 24C An isometric view of the medicine insert or an example of an insert in the receiving device shown. It should be understood that the circular insert 9100 is shown as an example to illustrate that an insert having this shape can be inserted into a hexagonal opening leading to a recess 3631 or 3651, wherein there is a contact point between the circular insert and the hexagonal opening leading to the recess. Inserts of any shape can be made and inserted into recesses in the plate of the receiving device.

[0430] The user can insert the eye-viewing device into the eye. The user can use a mechanism for storing and transporting the device for insertion into the eye. The eye-viewing device can be used with or without such a mechanism, and the eye-viewing device is not limited to use with such a mechanism.

[0431] case

[0432] This application discloses a housing that can be used as a mechanism for storing and conveying an eye-accessing device for insertion into the eye. The housing allows a user to retrieve the eye-accessing device conveyed by the housing for easy grasping and insertion into the eye. A housing for holding and dispensing an eye-accessing device is described, typically inserted and removed by a human finger for insertion into the user's eye. The human can be the user or someone such as a doctor, other eye care professional, or caregiver. The housing has an eye-accessing device that is grasped with fingers, wherein the device is oriented in a suitable three-dimensional orientation relative to the user for placement in the user's eye. The housing and its components may have tactile features to allow a visually impaired person to determine or confirm the orientation of the eye-accessing device for placement in the eye, to remove the device from the housing, and to insert the device knowing its orientation.

[0433] The housing may provide ports for introducing fluid to coat the receiving device within the housing. Gases, including air, may also pass through these ports. Fluid can be introduced without manipulating the housing or the receiving device within it.

[0434] The housing can dispense the receiving device from either side of the housing, thereby maintaining the orientation of the receiving device. For example, the housing can have a receiver with channels that open on both sides of the receiver, the channels being configured such that the receiving device can be dispensed from either side of the receiver without changing the orientation of the receiving device. As a result, the receiving device can be removed from the device using the fingers of either the left or right hand without needing to reorient the housing or reposition the receiving device once it has been removed from the housing.

[0435] The shell can be made of thermoplastic material (e.g., polypropylene thermoplastic material).

[0436] Figure 25A This is a perspective view of the housing 900 in its open position. The housing 900 includes a compartment 901. The compartment 901 is configured to retain fluid within its interior, which... Figure 25A The interior space 902 is shown in the middle. Compartment 901 is located in... Figure 25A The middle section is shown as having an elongated oval shape. It should be understood that the compartments can have a similar shape to... Figure 25A The different shapes shown depend on the shape of the receiving device to be held, the user's needs, and the desired shape of the housing 900. For example... Figure 25A As shown, compartment 901 has an open top.

[0437] The shell can be formed as a single piece of material. The shell can be made of a thermoplastic or thermosetting polymer exhibiting a yield elongation percentage (%) in the range of approximately 6% to 250% according to the ASTM D638 ISO 527-1 tensile test method. Features of the shell can be interrelated. Each feature of the shell can perform a different function. By way of example and not limitation, one or more features of the shell, or the entire shell, can be made of polypropylene thermoplastic material.

[0438] The shell can be manufactured using a relatively low-cost injection molding process.

[0439] The compartment 901 is connected to the stabilizer 904 at the joint 905. The compartment 901 can be connected to one side of the stabilizer 904 perpendicular to the joint 905. The connection between the compartment 901 and one side of the stabilizer 904 at the joint 905 can be achieved in many ways, and is not limited to these. Figure 25A The connection shown in the image. Figure 25AAs shown, stabilizer 904 forms a ring around compartment 901, and compartment 901 protrudes into the interior of the ring, such that compartment 901 is surrounded and protected by stabilizer 904.

[0440] Stabilizer 904 provides a position for holding housing 900. When dispensing the eyepiece, for example by placing a hand, part of a hand, or fingers on stabilizer 904, the housing can be secured in a generally flat position. Stabilizer 904 can stabilize housing 900 in a generally flat position, for example by preventing the housing from tipping over. Stabilizer 904 may include features that visually, tactilely, or otherwise indicate the orientation of the housing relative to the user from whom the eyepiece will be dispensed. For example, stabilizer may be individually or in combination marked with words, Braille, or colors to convey the message “place toward the user.”

[0441] The housing 900 includes a cover 906. The cover 906 is connected to a compartment 901 and is rotatable between a position where the housing is closed by covering the open top of the compartment and a position where the housing is open by leaving the compartment uncovered. The connection between the cover 906 and the compartment 901 can be a hinge. The hinge can be a movable hinge, wherein the material connecting the compartment 901 and the cover 906 is a single manufactured part that can flex back and forth. It should be understood that the compartment 901 and the cover 906 of the housing can be directly connected or connected with an intermediary material, which includes, for example, a portion of a stabilizer 904.

[0442] like Figure 25A As shown, cover 906 is a flat cover having a top and a bottom. Covers used in housings for access devices can include any combination of geometries, as long as the cover can cover the top of the compartment when in the position covering the open top of the compartment. For example... Figure 25A As depicted, cover 906 typically comprises two planar rectangles of different sizes to allow for easier identification and operation. The elongated planar rectangle near joint 905 covers the open top of compartment 901. When in the position covering the top of the compartment (see...) Figure 25B The planar rectangle on the far side of the joint 905 extends through the compartment 901, thereby allowing the user to remove the cover 906 from the top of the compartment 901 using the far planar rectangle and rotate the cover around the joint 905.

[0443] The housing may also include fasteners for removably securing the cover 906 to the open top of the covered compartment 901. For example, the fasteners may be a latch or a lock. Figure 25A As shown, the housing includes latches 907 / 903, which include a key 907 on the cover and a post 903 on a protrusion extending from the compartment 903. The key 907... Figure 25AThe gap in the cover 906 is depicted as such. The key 907 can be formed in a shape that allows engagement with the post 903 to removably secure the cover 906 to the open top of the covered compartment 901. (See image below.) Figure 25A As shown, post 903 is located on a protrusion originating from compartment 901 at the opposite end of the compartment relative to the joint 905. Post 903 extends from the protrusion extending from compartment 901, perpendicular to the protrusion. Post 903 may be cylindrical. It should be understood that the fastener may be a latch, an anchor, or other means of removably securing the cover to the compartment. The fastener may also be a friction fit between the cover and the compartment, or a feature on the cover or the compartment, or both. It should also be understood that the fastener component may be any part of the housing or any part added to the housing.

[0444] The housing may also include features for holding and dispensing the contact device. For example... Figure 25A As shown, the housing has a receiver 908 that extends from the cover 906 and is configured to receive and retain the contact device. The receiver 908 is positioned such that when the cover 906 is in the closed position, the receiver 908 is within the internal space 902 of the compartment 901, allowing any fluid in the compartment (such as fluid transmitted through port 909) to contact the contact device held in the receiver 908, and the contact device can be immersed in the fluid. The receiver 908 can be located near port 909 such that fluid entering port 909 flows through the contact device when the cover is in the closed position. Channels open on both sides of the receiver pass through the receiver 908. These channels can hold the contact device and are configured such that the contact device can be dispensed from either side of the receiver without altering its orientation. As a result, the contact device can be removed from the housing by pulling it away from the receiver using the fingers of a hand, without needing to reorient the housing or reposition the contact device once removed from the housing. Alternatively, when removing the contact device with the pull handle, a push handle can be used to guide the contact device toward the pull handle.

[0445] The channel in the receiver 908 can have any three-dimensional shape capable of receiving a receiving device. One side of the channel is defined by the top surface of the cover 906, and the other three sides are defined by the receiver. The channel is... Figure 25A It is shown as having openings at both ends.

[0446] Figure 25B yes Figure 25A The side view of housing 900 shown is longitudinally cut through the center of the housing. Cover 906 is positioned to cover the open top of the compartment, thus closing the housing. Figure 25BThe ridge 910 visible in the cut-open receiver is a constraint element configured to hold the receiver. It should be understood that the constraint element can be a ridge or other element configured to hold the receiver in a specific orientation or position and allow insertion and removal of the receiver. It should be understood that the receiver 908 can be of any geometry that permits it to receive, hold, and dispense the receiver.

[0447] Figure 25C yes Figure 25A The image shows a perspective view of the casing, with the cover in the closed position. (See image for reference.) Figure 25C As shown, post 903 engages with key 907, thereby removably securing cover 906 in a closed position and preventing liquid from entering or leaving the interior space 902 during operation of housing 900 except through port 909. The latch can be of any shape for the post and key, as long as friction between post 903 and key 907 removably secures cover 906 in the closed position when it is in the closed position. The cover and compartment may include additional features for forming a seal between the cover and compartment.

[0448] Cover 901 Figure 25B The compartment 901 is depicted as having a port 909. Port 909 is a gap in the cover 906. When the cover 906 is in the closed position, port 909 is in fluid communication with the interior space 902 of compartment 901, thereby allowing fluids, including liquids (such as solutions) and gases (such as air), to enter or exit the interior space 902 of compartment 901 through port 909. As an example, port 909 allows a solution to be added to the interior space 902 of compartment 901 of housing 900 without requiring the removal of cover 906 from compartment 901 to expose the interior space 902 or any means held within housing 900. Port 909 may be long enough to allow gases (such as air) to escape from the interior space 902 of compartment 901 and to allow liquids to enter the interior space 902 of compartment 901. Liquids and gases can be exchanged simultaneously through port 909.

[0449] Figure 25D yes Figure 25C The perspective view of the housing shown in the figure shows a removable peel strip 911 covering the port in the cover. The peel strip seals the port 909 of the compartment 901. Figure 25D In the middle, a portion of strip 911 was peeled off (in Figure 25DThe strip (marked 912) extends away from the cover surface to allow the stripping strip to be removed to expose the port. The stripping strip may be made of a material that provides a biobarrier for the sterilization of the chamber. When the cover is in the closed position and the stripping strip is in place, a sealed chamber is formed in the internal space 902 within compartment 901. It should be understood that any method can be used for the sterilization of the sealed chamber, including but not limited to gamma radiation, electron beam, steam, autoclave, and ethylene oxide (ETO). When the stripping strip is removed and the cover is in the closed position, fluid can be added to the housing through the port, and if the contact device is inside, the fluid will flow through the contact device.

[0450] The housing 900 may include a removable peel strip 911 covering the port 909. The removable peel strip 909 protects the interior space 902 and the contents of the receiver 910 from contamination and damage. The removable peel strip 911 can be peeled off from the cover 906 when a user needs to access the port 909. The removable peel strip 911 may include a pull tab 912 detached from the cover 906. The pull tab 912 allows the peel strip 911 to be removed by gripping and removing it. In addition to protecting the interior space 902, the peel strip is tamper-proof and provides an alarm for possible tampering. Other tamper-proofing devices and alarms, such as release tape, may be adapted to the housing.

[0451] The contact device can be sterilized in a sealed chamber. It should be understood that any method can be used for sterilization of the contact device in a sealed chamber, including but not limited to gamma radiation, electron beam, steam, autoclave, and ethylene oxide (ETO).

[0452] Figure 26A This is a perspective view of the housing 1990, which retains an example of the receiving device marked 2126, with the cover 1906 in the open position. It should be understood that the housing 1990 is not limited to... Figure 26A The specific receiving device 2126 shown is used together. The receiver may include a channel open on at least one side of the receiver. For example... Figure 26A As shown, the channels in receiver 1908 are open on both sides of the receiver.

[0453] Figure 26B This is a perspective view of an example of a closed housing holding a receiving device (not shown), wherein port 1909 is not covered in order to introduce fluid into the compartment, through the receiving device.

[0454] Figure 26C This is a perspective view of an open housing containing an example of a receiving device, with the receiving device protruding from the side of the receiver away from the compartment.

[0455] Figure 26DThis is a perspective view of an open housing containing an example of a receiving device, with the receiving device protruding from the receiver near the compartment.

[0456] Figure 26A This is a schematic diagram illustrating an example embodiment of the housing 1990 in the open position, wherein the housing 1990 retains the example embodiment of the receiving device 2126, and Figure 26B This is a schematic diagram illustrating an example embodiment of a housing 1990 in a closed position, which holds the eye-viewing device 2126 in an example embodiment. The housing 1990 is positioned in a generally flat location in front of the user, with the surface of the eye-viewing device 2126 facing the user and in contact with the sclera of the eye. Figure 26B As shown, embodiments of the invention allow the receiving device 2126 to be held within the internal space 1902 by the receiver 1908 when the cover 1906 is in the closed position covering the compartment 1901. The post 1903 and key 1907 can be interconnected to secure the cover 1906 in the closed position. The housing 1990 can be in a position where... Figure 26B The device is delivered to the user in the closed position shown in the diagram, wherein the eyepiece 2126 is protected and held in the desired orientation. When the user receives the housing 1990, the housing 1990 is configured to allow the user to orient the eyepiece 2126 in a specific orientation and / or position that facilitates the proper insertion of the eyepiece 2126.

[0457] Users can rotate the cover 1906 from the open top position covering the compartment to Figure 26A The open position is shown in the diagram. When the cover 1906 is in the open position, the receiver 1908 delivers the eye-contact device 2126 to be inserted into the eye. It should be understood that the eye-contact device 2126 may require a specific orientation for proper insertion into the eye, or a specific orientation may be preferred. The receiver 1908 can be configured to hold the eye-contact device 2126 and cause it to be in a specific orientation. When the housing 1903 is placed on a table or other generally flat surface, the orientation of the eye-contact device 2126 is determined by the orientation of the housing 1990. As a result, the orientation of the housing 1990 is controlled to determine and control the orientation of the eye-contact device 2126. The housing 1990 can be oriented relative to the user such that the eye-contact device 2126 is correctly oriented for insertion into the user's eye. With the housing correctly oriented relative to the user, the cover 1906 is rotated to the open position to deliver the eye-contact device 2126, the eye-contact device 2126 is removed from the receiver 1908, and the eye-contact device is inserted into the user's eye, thereby maintaining the orientation of the eye-contact device relative to the user.

[0458] Figure 26CThis is a schematic diagram illustrating an example embodiment of the housing 1990 in the open position, with the housing 1990 held in place on the side of the receiver 1908 away from the compartment, and the receiving device 2126 protruding from the receiver 1908. Figure 26D This is a schematic diagram illustrating an example embodiment of the housing 1990 in the open position, with the housing 1990 held in place by an example embodiment of the receiving device 2126 protruding from the receiver 1908 on the side of the receiver near the compartment. (As...) Figure 26C and Figure 26D As shown, the eye-receiving device 2126 can be removed from the receiver 1908 through either open side of the receiver 1908. The user can use a pull handle to grasp the protrusion of the eye-receiving device 2126 from the proximal or distal side. The user can also use a push handle to guide the protrusion of the eye-receiving device 2126 toward the pull handle. Because the eye-receiving device 2126 can be inserted or removed through either open side of the receiver 1908, the housing 1990 can be held at multiple angles, and the eye-receiving device can be accessed by either hand of the user. This allows the user to choose their preferred hand and grip when performing delicate tasks such as manipulating and / or inserting the eye-receiving device 2126.

[0459] The housing 1990 may include tactile and visual features to enable a user to identify the orientation of the viewing device 2126 without opening the cover 1096 of the housing 1990 and exposing the viewing device 2126. The housing 1990 may be larger than the viewing device 2126 so that the orientation can be obvious, even if the orientation of the viewing device itself is not obvious. The orientation of the housing 1990 can be used to determine the orientation of the viewing device 2126, rather than directly inspecting the viewing device 2126, thereby reducing the risk of misidentifying the orientation and the risk of device misalignment due to incorrect orientation. The positioning of the housing, stabilizer 1904, cover 1906, and / or receiver 1908 visually, tactilely, or otherwise indicates to the user the correct orientation of the viewing device 2126.

[0460] like Figure 26C and Figure 26D As shown, the delivery receiving devices 2126 from opposite sides of the receiver allow the device to be removed from either side of the housing while being pulled away by either hand. Alternatively, the device can be pushed in using a different hand than the one used to pull it. Figure 26C or Figure 26D The location shown in the image.

[0461] Figure 27AThis is a schematic diagram illustrating an example embodiment of a kit, which includes a housing 1990 holding an eye contact device (not shown) and a substance to be applied to a user's eyes. The kit includes the housing 1990, the substance to be applied to the user's eyes contained in a bottle 2400, and the eye contact device. The substance to be applied to the eyes can be, for example, a wetting solution, a medicine, or a drug. The kit can be combined with a sterile bag (not shown) configured to hold and protect the housing 1990. The sterile bag can consist of a plastic cap attached to a biobarrier bottom membrane, the cap having seals along all edges of the cap. This peripheral seal ensures that the housing 1990 and any contents within it remain within the bag during transport and serves as proof that the sterilization of the housing 1990 has been maintained. The bag seal can be configured such that a user can tear open at least one edge to expose the housing. As an example, a commercially available Tyvek bag can be used. The kit may also include a sealed housing 1990 with biological barriers (such as a peel strip for a sealed port), a substance to be applied to the user's eyes in a vial 2400, and an eye-contact device in the sealed housing (see [link to kit]). Figure 25D The material to be applied to the eye can be, for example, a wetting solution, a medicine, a pharmaceutical product, or a combination of these substances.

[0462] Figure 27B This is a schematic diagram illustrating an example implementation of the kit, where a substance is being applied to the contact device within the housing. In this particular example, the user pours liquid 2405 through port 1909. During this process, housing 1990 remains in a closed position, and the contact device inside remains covered, with the port in fluid communication with the interior of the compartment. The contact device within housing 1990 is immersed in the liquid as liquid 2405 flows through port 1909 and fills the compartment of housing 1990. Air escaping from housing 1990 can also flow through port 1909. The contact device within housing 1990 is coated with liquid 2405.

[0463] Terms such as “convex,” “toroidal,” and “sphere” are expressive tools used to describe the properties and interactions of the disclosed apparatus and eye anatomy, and to inform the relationships of surface interactions, and do not imply a limitation on the precise geometry of the disclosed eye-connecting apparatus.

[0464] The recesses and drug inserts shown in the figures are intended to illustrate possible features for the purpose of simplifying the description and are not intended to be limiting in any way.

[0465] It should be understood that terms describing geometric shapes and relationships will not be considered as mathematical descriptions of any apparatus or feature with mathematical precision.

[0466] Insert composition and manufacturing method

[0467] Any number of inserts can be placed into the eye-receiving device described herein, particularly when made of a geometry permissible for placement within the eye-receiving device. Typically, the inserts contain one or more pharmaceutically active agents and pharmaceutically acceptable carriers. Using more than one pharmaceutically active agent can provide, for example, the release of a pharmaceutically active agent that can simultaneously treat more than one eye condition.

[0468] Therefore, this document provides compositions comprising one or more pharmaceutically active agents and pharmaceutically acceptable carriers (e.g., ocular-compatible carriers) (e.g., pharmaceuticals such as eyes, compositions, or insert compositions). In some embodiments, the pharmaceutically acceptable carrier forms a matrix, and one or more pharmaceutically active agents are dispersed (e.g., uniformly dispersed) within the matrix. In some embodiments, the matrix comprises one or more polymers (e.g., blends of two or more polymers such as water-soluble and water-insoluble polymers). For example, pharmaceutically active agents for inserts in eye contact devices can have various compositions, structures, and properties, including but not limited to ciprofloxacin, dexamethasone, olopatadine, pilocarpine, hyaluronic acid, and hydroxypropyl cellulose, as well as their pharmaceutically acceptable salts. Pharmaceutically active agents may include agents required for short-term, long-term, or short- and long-term treatment of the eye. Examples of eye conditions that can be beneficially treated with the devices and compositions described herein include dry eye, glaucoma, allergies, infections (e.g., bacterial, viral, and other infections), chronic inflammatory conditions such as acne rosacea keratitis, circinitis, and blepharitis, selective retinal conditions such as diabetic retinopathy, age-related macular degeneration and other retinal conditions, postoperative infections, and amblyopia.

[0469] Categories of pharmaceutically active agents that can be used to treat the conditions mentioned above include steroids, anti-inflammatory drugs, antibiotics, glaucoma treatment compounds, antihistamines, dry eye medications, neuroprotective agents, retinoids, antiangiogens, antioxidants, antimuscarinic drugs, and biologics. Examples of steroids include glucocorticoids, progestins, amine corticosteroids, and corticosteroids. Exemplary corticosteroids include cortisone, hydrocortisone, prednisolone, methylprednisolone, triamcinolone, flumethasone, dexamethasone, metoprolol, betamethasone, loteeprednisolone, fluocinolone acetonide, dexamethasone, vermicelli, and mometasone. Other examples of steroids include androgens such as testosterone, methyltestosterone, or danazol. Examples of anti-inflammatory drugs include NSAIDs such as piroxicam, aspirin, amigesic, dolobid, ibuprofen, ketoprofen, relaxon, feldene, naproxen (Aleve), diclofenac, indomethacin, sullinic acid, tolectin, lodine, toradol, oxaprazin (Daypro), and celecoxib. Examples of antibiotics include amoxicillin, penicillin, sulfonamides, erythromycin, streptomycin, tetracycline, clarithromycin, teconazole, azithromycin, bacitracin, ciprofloxacin, edofloxacin, ofloxacin, levofloxacin, moxifloxacin, gatifloxacin, aminoglycosides, tobramycin, and gentamicin, as well as polymyxin B combinations including polymyxin B / trimethoprim, polymyxin B / bacitracin, and polymyxin B / neomycin / bacitracin. Glaucoma treatments include beta-blockers such as timolol, betalol, levobetaclopramide, and carteolol; generic drugs such as pilocarpine; carbonic anhydrase inhibitors such as brinzolamide and dzodamide; prostaglandins such as travoprost, bimatoprost, and latanoprost; serotonergics; muscarinic acid; dopaminergic agonists; and adrenergic agonists such as ameronine and brimonidine, as well as prostaglandins or prostaglandin analogues such as latanoprost, bimatoprost, and travoprost. Antihistamines and mast cell stabilizers include olopatadine and ebiustin; acute care anti-allergy products include ketotifen fumarate, lotidine, ebiustin hydrochloride, emestin fumarate, azelastine hydrochloride, olopatadine hydrochloride, and ketotifen fumarate; while chronic care anti-allergy products include pirostemma pentahydrate, nalorometazone sodium, lolodoxamine tromethamine, and sodium cromoglycate. Antimuscarinic drugs include atropine, scopolamine, tropicamide, ipratropium bromide, and glycopyrronium bromide used to control myopia.Antiangiogenic agents include the biologics ranibizumab (Lucentis) and bevacizumab (Avastin). Amblyopia treatment includes anesthetics and cycloplegic agents such as atropine. Treatment for retinitis pigmentosa can be achieved with N-acetylcysteine, N-acetylcysteine ​​amide, and neretidine (neretidine). Dry eye medications include cyclosporine and lifitegrast, as well as eye lubricants such as methylcellulose, sodium carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, and hydroxypropyl methylcellulose, polyethylene oxide, polyethylene glycol, and hyaluronic acid. Any of the aforementioned agents may exist in the form of a free base or as a pharmaceutically acceptable salt of their respective composition.

[0470] Other examples of pharmaceutically active agents include nerve growth factor (e.g., human nerve growth factor), platelet-derived growth factor, transforming growth factor, fibroblast growth factor (e.g., human fibroblast growth factor), growth hormone (e.g., human growth hormone), neurotrophic factor-3, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, platelet activating factor (PAF, e.g., PAF receptor agonists and / or antagonists), tumor angiogenesis factor, albumin, β-lactoglobulin, and bovine serum albumin. Albumin, gamma globulin, monoclonal immunoglobulins, immunoglobulin G, ovalbumin, insulin, monoclonal antibodies (e.g., anti-hCG), alkaline phosphatase, tumor-associated antigens, catalase, ferritin, prolactin and its mutants, anti-horseradish peroxidase, prolactin and its mutants, macrophage inflammatory protein 3β, platelet-reactive protein, trypsin, soybean trypsin inhibitor, DNA, high molecular weight reporter plasmids, RNA, heparin, lipopolysaccharide, GRGDSP peptide, and leuprorelin, and their pharmaceutically acceptable salts. In Schneider, C. et al. Journal of Controlled Release (262 (2017), 284-295) and Schneider, C. et al. Journal of Controlled Release Pharmaceutical active agents, for example, used with EVA copolymers, are described in (278 (2018), 156-158), the contents of which are incorporated herein by reference.

[0471] In some embodiments, the pharmaceutical active agent includes an anti-allergic and / or antihistamine compound, for example, to prevent allergic reactions to the ocular insert composition. In the compositions described herein, the anti-allergic and antihistamine compounds are typically used in combination with another pharmaceutical active agent. Therefore, in some embodiments, the composition includes a first pharmaceutical active agent and a second pharmaceutical active agent, wherein the second pharmaceutical active agent is an anti-allergic and / or antihistamine compound.

[0472] In some embodiments, the pharmaceutical active agent has a melting temperature greater than about 99°C. In some embodiments, the pharmaceutical active agent is water-soluble. In some embodiments, the pharmaceutical active agent has a melting temperature higher than about 99°C and is water-soluble.

[0473] As used in this article, “water-soluble” means that 1 part (volume) of solute needs to be dissolved in 10,000 parts (volume) or less of an aqueous medium (usually water, but sometimes a buffer). The following table describes various solubility levels.

[0474]

[0475] In some embodiments, the pharmaceutical active agent is very soluble, readily soluble, soluble, slightly soluble, or very slightly soluble in an aqueous medium (e.g., water).

[0476] In particular, when a pharmaceutical active agent is incorporated into a composition using hot melt blending as described herein, the pharmaceutical active agent will typically be in the form of microparticles and / or nanoparticles. Therefore, in some embodiments, the pharmaceutical active agent is in the form of particles (e.g., microparticles, nanoparticles). In some embodiments, the pharmaceutical active agent has a melting temperature above about 99°C, is water-soluble, and is in particulate form.

[0477] Typically, the pharmaceutical active agent accounts for about 0.1% to about 99% of the composition by weight, for example, about 0.1% to about 75%, about 0.1% to about 50%, about 0.5% to about 50%, or about 1% to about 40%.

[0478] As an example, and not a limitation, inserts for delivering pharmaceutical active agents include those disclosed in the following U.S. patents (the entire teachings of which are incorporated herein by reference): U.S. Patent No. 3,302,646 (Behney), U.S. Patent No. 3,416,530 (Ness), U.S. Patent No. 4,309,996 (Theeuwes), U.S. Patent No. 6,071,266 (Kelley), U.S. Patent No. 6,331,313 (Wong), U.S. Patent No. 7,211,272 (Renner), U.S. Patent No. 8,167,855 (Leahy), U.S. Patent No. 8,287,504 (Leahy), U.S. Patent No. 8,574,659 (Ashton), U.S. Patent No. 8,679,078 (Leahy), and U.S. Patent No. 8,939,948 (de Juan), U.S. Patent No. 9,005,649 (Ho), U.S. Patent No. 9,421,126 (de Juan), U.S. Patent No. 9,549,846 (Clauson), U.S. Patent No. 9,750,636 (de Juan), U.S. Patent No. 9,814,671 (Lee), U.S. Patent No. 9,849,085 (Ashton), U.S. Patent No. 9,931,306 (Barman), and U.S. Patent No. 9,937,073 (de Juan).

[0479] As used herein, the term "pharmaceutically acceptable" means, within reasonable medical judgment, suitable for use in contact with the tissues of mammals without excessive toxicity, irritation, allergic reactions, etc., and in proportion to a reasonable benefit / risk ratio. For example, a substance is pharmaceutically acceptable (in the amount used according to the administration regimen in the dosage form) and in proportion to a reasonable benefit / risk ratio when it is suitable for use in contact with the cells, tissues, or organs of animals or humans without excessive toxicity, irritation, allergic reactions, immunogenicity, or other adverse reactions.

[0480] As used herein, the term "pharmaceutically acceptable salt" refers to those salts which, within reasonable medical judgment, are suitable for use in contact with mammalian tissues without excessive toxicity, irritation, allergic reactions, etc., and in proportion to a reasonable benefit / risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, SM Berge et al. described pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences (1977, 66, 1-19), the entire teachings of which are incorporated herein by reference. Pharmaceutically acceptable salts include salts derived from suitable inorganic and organic acids, as well as suitable inorganic and organic bases.

[0481] Examples of pharmaceutically acceptable acid addition salts are salts of amino groups formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid, or with organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid, or by other methods such as ion exchange used in the art. Other pharmaceutically acceptable acid addition salts include adipates, alginates, ascorbic acid salts, aspartate salts, benzenesulfonates, benzoates, hydrogen sulfates, borates, butyrates, camphorates, camphorsulfonates, cinnamates, citrates, cyclopentanepropionates, digluconate, dodecyl sulfates, ethanesulfonates, formates, fumarates, glucono-p-ethylhexanoates, glycerophosphates, gluconates, glutarates, glycolates, hemisulfates, heptahydrates, hexanoates, hydroiodates, hydroxybenzoates, and 2-hydroxy-ethanesulfonates. Hydroxymaleate, lactobionate, lactic acid, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, dihydroxynaphthalate, pectate, persulfate, 2-phenoxybenzoate, phenylacetate, 3-phenylpropionate, phosphate, neopentanoate, propionate, pyruvate, salicylate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate, etc. These salts can form mono-, di-, or tri-acid salts, and can exist in hydrated, solvated, or essentially anhydrous forms.

[0482] Salts derived from suitable bases include those derived from inorganic bases such as alkali metals, alkaline earth metals, and ammonium bases, as well as those derived from aliphatic, alicyclic, or aromatic organic amines such as methylamine, trimethylamine, or methylpyridine, or N((C1-C4)alkyl)4 salts. Representative alkali metal or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and barium. Where appropriate, other pharmaceutically acceptable salts include non-toxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halides, hydroxides, carboxyl groups, sulfates, phosphates, nitrates, lower alkyl sulfonates, and aryl sulfonates.

[0483] In one embodiment, the composition (e.g., a pharmaceutical composition such as an ophthalmic composition) comprises one or more pharmaceutically active agents and a water-insoluble polymer (e.g., EVA according to any embodiment described herein). In some embodiments, the composition also comprises a water-soluble polymer (e.g., PEO according to any embodiment described herein). In some embodiments, for example, according to DSC ASTM D2417, the water-insoluble polymer has a melting point below about 99°C. In some embodiments, for example, according to DSC ASTM D2417, the water-soluble polymer has a melting point below about 99°C. In some embodiments, for example, according to DSC ASTM D2417, the water-soluble polymer and the water-insoluble polymer together have a processing-formed melting point below about 99°C. Typically, in this embodiment, the water-soluble polymer and the water-insoluble polymer form a matrix in their presence, and one or more pharmaceutically active agents are dispersed (e.g., uniformly dispersed) within the matrix.

[0484] This document also provides matrices (e.g., for delivering one or more pharmaceutical active agents) comprising water-insoluble polymers (e.g., EVA according to any embodiment described herein) and water-soluble polymers (e.g., PEO according to any embodiment described herein).

[0485] Without being bound by any particular theory, it is believed that the water-insoluble polymers in the matrix and compositions described herein act as a scaffold to impart shape and stability to the compositions. Additionally, it is believed that the water-insoluble polymers can prevent the pharmaceutical active agents in the matrix from escaping from the matrix.

[0486] Non-limiting examples of water-insoluble polymers include ethylene vinyl acetate (EVA). EVA is a copolymer of ethylene and vinyl acetate and can be represented by the following structural formula describing a block copolymer of EVA: In this expression, n and m represent the weight percentages of ethylene and vinyl acetate in the copolymer, respectively, and the sum of n and m is 100%. Typically, m is 25% or greater (e.g., 28%, 40%). In some embodiments, according to ASTM D638, for example, EVA has a tensile elongation of 750% or greater. In some embodiments, according to ASTM D1238, for example, EVA has a melt flow index of 6.0 g / 10 min or greater. In some embodiments, for example, according to DSC ASTM D2417, EVA has a melting point below about 99°C.

[0487] Typically, the water-insoluble polymer in the composition is present in a weight percentage of about 5% to about 99%, about 20% to about 75%, about 25% to about 75%, or about 20% to about 50%.

[0488] It should be understood that tears are aqueous liquids. Water-soluble polymers (at least partially) dissolve in aqueous fluids such as tears. Therefore, when exposed to aqueous fluids, the water-soluble polymers present in the compositions described herein are expected to dissolve (at least partially), thereby eroding from the composition. It is desirable that the inclusion of water-soluble polymers in the compositions described herein enhances the dissolution and erosion of the pharmaceutical active agent in the composition, resulting in faster erosion of the pharmaceutical active agent than in the absence of water-soluble polymers. The transport rate of each pharmaceutical active agent is a direct factor in the solubility of individual particles in the reagent. Therefore, the particles of each reagent (whether individually or in inserts) will be dispersed independently, each reagent at its own rate. When water-soluble polymers are present, the water-soluble polymers transport one or more pharmaceutical active agents dispersed therein. Therefore, the rate of reagent delivery per unit time can be large and can be adjusted and / or controlled during manufacturing by adjusting component relationships.

[0489] Non-limiting examples of water-soluble polymers include polyethylene oxide (Polyox or PEO), also known as polyethylene glycol (PEG). In some embodiments, the molecular weight of PEO is from about 100,000 to about 300,000 (e.g., about 100,000, about 200,000, about 300,000). In some embodiments, PEO has a viscosity of about 10 CPS to about 20,000 CPS (e.g., 5% H2O at C=25°C) at a concentration of about 5% by weight in water at about 25°C. In some embodiments, about 96% to about 100% of the PEO is in the form of 20-mesh particles. In some embodiments, PEO has a melting point of less than about 99°C. Without wishing to be bound by any particular theory, it is believed that the presence of polyethylene oxide in the compositions or delivery matrices described herein (particularly matrices for application to the eyes) can suppress allergic reactions to the compositions in subjects such as patients. Eluting polyethylene oxide along with the pharmaceutical active agent can prevent protein adhesion, thus minimizing the chance of an allergic reaction. Polyethylene oxide can also provide lubrication for the eyes.

[0490] Typically, the water-insoluble polymer (when present) in the composition is present in a weight percentage of about 1% to about 90%, for example, about 1% to about 75%, about 1% to about 50%, about 2.5% to about 85%, about 5% to about 80%, about 25% to about 80%, or about 40% to about 75%.

[0491] The compositions and matrices described herein can be prepared by hot-melt blending the components of the composition or matrix to form a hot-melt blend. The hot-melt blend can then be shaped and / or cooled. The resulting shaped composition or matrix is ​​also referred to herein as an insert.

[0492] Therefore, a method for preparing a composition (e.g., a medicament such as an ophthalmic composition) is also provided herein, the method comprising: hot-melt blending one or more pharmaceutically active agents and a pharmaceutically acceptable carrier (e.g., one or more polymers such as a blend of two or more polymers; a water-insoluble polymer; a water-insoluble polymer and a water-soluble polymer) to form a hot-melt blend; and cooling the hot-melt blend. In some embodiments, the method further comprises shaping the hot-melt blend. In some embodiments, the method comprises hot-melt blending one or more pharmaceutically active agents, a water-insoluble polymer (e.g., EVA according to any embodiment described herein), and a water-soluble polymer (e.g., PEO according to any embodiment described herein) to form a hot-melt blend.

[0493] This document also provides a method for preparing a matrix (e.g., for delivering one or more pharmaceutical active agents), the method comprising: hot melt blending a water-insoluble polymer (e.g., EVA according to any embodiment described herein) and a water-soluble polymer (e.g., PEO according to any embodiment described herein) to form a hot melt blend; and cooling the hot melt blend. In some embodiments, the method further comprises shaping the hot melt blend.

[0494] Advantageously, the therapeutic agent maintains its integrity during manufacturing, including melt processing, for example, as a particulate or nanoparticle-like structure dispersed within the blended polymer matrix. This may be most useful for delivering agents that may have minimal solubility in tears and require more residence time for transport across septal tissues, and / or where retention by the user's natural tears is practically minimal. Therefore, typically, in the methods described herein, hot melt blending is performed at a sufficiently low melting temperature (e.g., below about 99°C, below the melting temperature of the pharmaceutical active agent) without affecting the structure and / or properties of the active pharmaceutical ingredient. Thus, in some embodiments, the components of the matrix (e.g., water-insoluble polymers and / or water-soluble polymers) obtained independently or together have a processing-formed melting point of about 99°C or lower (e.g., 99°C or lower) and / or below the melting temperature of the pharmaceutical active agent. In some embodiments, hot melt blending is performed at temperatures below about 99°C (e.g., below 99°C). In some embodiments, hot melt blending is performed at a temperature below the melting temperature of one or more pharmaceutical active agents (e.g., 25°C, 50°C, 75°C, 100°C or higher, below the melting temperature).

[0495] Pharmaceutical active agents typically have a melting point (Mp) above 99°C. For example, ciprofloxacin has a melting point of 318°C to 320°C, dexamethasone has a melting point of 262°C to 264°C, and olopatadine has a melting point of 242°C to 245°C.

[0496] In use, an insert comprising one or more pharmaceutically active agents can be placed in the eye-contact device, and the assembled eye-contact device can be placed in the eye, under the eyelid, to deliver one or more pharmaceutically active agents to the eye. As an example, the insert can be shaped as a cylinder or rod. Alternatively, the insert can be in the form of a membrane or other configuration.

[0497] Without wishing to be bound by any particular theory, the following is a description of the steps believed to occur when a pharmaceutically active agent is delivered to the eye from an eye-mounting device containing the composition or insert described herein. When the insert loading device is placed in the eye, for example, under the lower eyelid (lower eyelid), it comes into contact with the tear film. The tear film permeates the surface of the insert and begins to dissolve the water-soluble polymer, exposing the pharmaceutically active agent to the tear film, which in turn begins to dissolve the pharmaceutically active agent. The dissolution of the water-soluble polymer also frees up space within the insert (which has been replaced by tear film in the matrix), allowing particles of the pharmaceutically active agent to be released and transported from the insert and / or device to the tear retention area across the surface of the ocular septum. Thus, the water-soluble polymer and the pharmaceutically active agent are slowly released from the eye-mounting device into the eye. Following the first-order drug delivery system, the natural tear film continues to transport particles of the pharmaceutically active agent at a decreasing concentration. It is anticipated that the water-insoluble polymer maintains the geometry of the insert, ultimately becoming a scaffold comprising the water-insoluble polymer and the retained tear film. As the dissolution process continues, the insert may swell, but the scaffold formed by the water-insoluble polymer provides stability and prevents rupture. The release of water-soluble polymers can provide the additional benefit of lubricating the eye. Furthermore, water-soluble polymers such as PEO can strengthen the mucin layer, the deepest layer of the tear film, which adheres to the underlying epithelial cells of the cornea and conjunctiva.

[0498] Dispersion matrices such as those described in this paper typically have three release mechanisms, which are generally effective: Drug diffusion from non-degradable polymers (diffusion control system). Drug release due to polymer degradation and erosion (erosion control system), and Enhanced drug diffusion due to polymer swelling (swelling control system).

[0499] The studies of various drugs incorporated into drug inserts described in this paper show that, for the early stages of drug release, the release kinetics appear to follow the Higuchi model.

[0500] The compositions described herein are particularly suitable for application to the eyes.

[0501] However, the compositions described herein can also be administered orally, parenterally (including subcutaneously, intramuscularly, intravenously, intradermally, by inhalation, topically, rectally, nasally, and vaginally), or orally, or via an implanted reservoir. As used herein, the term “parenterectomy” includes subcutaneous, intradermal, intravenous, intramuscular, intraocular, intravitreal, intra-articular, intra-articular, intrasynovial, intrasternal, intrasheath, intralesional, intrahepatic, intraperitoneal, and intracranial injection or infusion techniques.

[0502] As used herein, “local application” means applying a substance to one or more specific sites on or within a subject’s body, regardless of the site of action of the substance, if any. Therefore, formulations including the formulation matrix described herein can have local or systemic effects. Non-limiting examples of local application routes include transdermal, mucosal (e.g., oral, nasal, vaginal, urethral), sublingual, buccal, nasal, and ocular routes.

[0503] The described compositions are particularly suitable for application in contact with bodily fluids such as tears, rectal fluid, and saliva. Therefore, in some embodiments, the compositions described herein are applied to the mucous membranes (e.g., oral, nasal, vaginal, urethral mucosa), sublingual, cheek, nose, and / or eyes of a subject.

[0504] The compositions described herein can be any dosage form suitable for the intended method of administration. For example, the compositions described herein can be in the form of a semi-erodible polymer matrix, for example, for ophthalmic application. The compositions described herein can also be in a solid form, for example, for ophthalmic application. The compositions provided herein can be taken orally in any orally acceptable dosage form, including but not limited to solid dosage forms (e.g., capsules, tablets, pills, powders, granules), aqueous suspensions, dispersions, and solutions. Compositions suitable for oral or sublingual administration include tablets, lozenges, and tablet tablets. For rectal or lower ileum administration, the formulation can be in the form of a suppository. Suppositories are typically formulated with a suitable non-irritating excipient that is solid at room temperature but liquid at rectal temperature and thus melts in the rectum. Such excipients include cocoa butter, beeswax, and polyethylene glycol. For ophthalmic use, the formulation can be provided as a micronized suspension in isotonic, pH-adjusted sterile saline, or preferably as a solution in isotonic, pH-adjusted sterile saline, with or without preservatives such as benzyl chloride. Alternatively, for ophthalmic use, the formulation may be formulated as an ointment, for example, containing petrolatum. For nasal administration (e.g., inhalation), the formulation may be prepared as a solution in saline, using benzyl alcohol or other suitable preservatives, absorption enhancers to improve bioavailability, fluorocarbons, and / or other conventional solubilizers or dispersants.

[0505] The compositions described herein may also include excipients (e.g., pharmaceutically acceptable excipients) to enhance the stability or other physical properties of the composition. Typically, such excipients are non-biologically active, meaning they are, for example, non-substantial or non-biologically active and / or produce non-substantial or non-biological effects in the amount administered. Examples of excipients include preservatives, flavor enhancers, diluents, solvents, glycerin, gelatin, albumin, lactose, starch, stabilizers, melts, emulsifiers, suspending agents, salts, and buffers. Excipients may be organic or inorganic.

[0506] The compositions described herein can be formulated for immediate or non-immediate release, such as delayed release, sustained release, or prolonged release. The compositions described herein can also be formulated to provide controlled release of the pharmaceutically active agent contained herein. In some embodiments, the compositions described herein are formulated for prolonged release, for example, over about 12 hours, about 24 hours, about 36 hours, about 48 hours, about 72 hours, about 96 hours, about 5 days, about 6 days, or about 7 days. In some embodiments, the compositions described herein are formulated for release over about 12 hours to about 48 hours (e.g., about 12 hours, about 24 hours).

[0507] The amount of the active pharmaceutical ingredient in a single dosage form will vary depending on the subject being treated, the specific administration method, and the activity of the agent used. Preferably, the composition should be formulated such that a compound or a pharmaceutically acceptable salt thereof can be administered to a subject receiving the composition at a dose of about 0.01 mg / kg to about 100 mg / kg body weight / day. For example, in some embodiments, the dose may be in the range of about 0.5 mg / kg to about 100 mg / kg body weight, or alternatively, in the range of about 1 mg / dose to about 1000 mg / dose. Other suitable doses may be about 0.001 mg / kg to about 100 mg / kg, about 0.01 mg / kg to about 10 mg / kg, or about 0.01 mg / kg to about 1 mg / kg body weight per treatment. In some embodiments, the composition is formulated such that the dose of the active pharmaceutical ingredient described herein can be administered to a subject receiving the composition.

[0508] The desired dosage can be conveniently administered as a single dose, for example, so that the reagent is administered once daily, as in routine eyewear applications, or as multiple doses administered at appropriate intervals, for example, so that the reagent is administered 2, 3, 4, 5, 6 or more times daily. The daily dose can be divided, especially when a relatively large amount is administered, or, as needed, divided into multiple administrations (e.g., 2, 3, 4, 5, 6 or more).

[0509] It should also be understood that the specific dosage and treatment regimen for any particular subject will depend on a variety of factors, such as the activity of the specific reagent used, age, weight, general health, sex, diet, timing of administration, excretion rate, drug combination, the attending physician's judgment, and the severity of the specific disease, disorder, or condition being treated. The amount of reagent in the composition will also depend on the specific reagent in the composition. Determining the dosage for a specific reagent, subject, and disease, disorder, or condition is entirely within the capabilities of those skilled in the art. Preferably, the dosage does not cause or produces minimal adverse side effects.

[0510] Treatment

[0511] The devices and inserts described herein can be used to treat eye conditions. Therefore, methods for treating eye conditions in subjects in need are also provided herein, comprising administering to the subject a therapeutically effective amount of the compositions described herein. Examples of eye conditions that can be beneficially treated with the devices and compositions described herein include dry eye, glaucoma, allergies, infections (e.g., bacterial, viral, and other infections), chronic inflammatory conditions such as acne rosacea keratitis, circinitis, and blepharitis, selective retinal conditions such as diabetic retinopathy, age-related macular degeneration and other retinal conditions, postoperative infections, and amblyopia. Pharmaceutical active agents that can be used to treat these conditions are as described throughout the document.

[0512] As used herein, “treatment” refers to the steps of delivering an agent to a subject to achieve a desired or beneficial outcome (e.g., by administering one or more therapeutic agents to the subject). Non-limiting examples of beneficial outcomes include suppressing a disease or condition (e.g., by slowing or stopping its progression or causing the disease or symptoms to subside) and alleviating one or more symptoms caused by the disease or condition. Those skilled in the art can identify beneficial outcomes specific to the particular disease or condition to be treated.

[0513] As used herein, “administration” means taking steps to deliver a reagent to a subject, such as a mammal, when needed (e.g., by administering one or more active pharmaceutical agents to a mammal). Administration can be performed, for example, once, multiple times, and / or over one or more extended periods. Administration includes both direct administration (including self-administration) and indirect administration (including prescribing). For example, as used herein, a physician instructing a patient to administer the drug themselves or by another patient and / or prescribing the drug to a patient is administering the drug to the patient. Administration routes consistent with the compositions and methods described herein are as described in the context of insert compositions.

[0514] A “therapeutic effective dose” is the amount that effectively achieves the desired therapeutic outcome (e.g., treatment, suppression, or improvement of a disease or symptom) within the necessary dosage and time period. A complete therapeutic effect does not necessarily occur with the administration of a single dose and may only occur after a series of doses. Therefore, a therapeutic effective dose can be administered in one or more administrations. Therapeutic effective doses can vary depending on factors such as the mammal's disease state, age, sex, and weight, the mode of administration, and the ability of the therapeutic agent or combination of therapeutic agents to elicit the desired response in an individual. Therapeutic effective doses of the agent to be administered can be determined by a person skilled in the art using the guidance provided herein and other methods known in the art.

[0515] As used herein, "subject" refers to a mammal and includes humans and non-human mammals such as dogs, monkeys, pigs, rats, mice, cats, dogs, rabbits, cattle, sheep, goats, and horses. "Patient" refers to a human subject. In some embodiments, the subject is a human.

[0516] Example

[0517] Example 1. Insert preparation

[0518] Inserts were prepared and tested using a composition comprising the percentage of water-insoluble polymer [A] (A%), the percentage of water-soluble polymer [B] (if any) (B%), and the percentage of [C] (C%) used to evaluate the pharmaceutical product of interest as indicated in the table below. Components [A], [B], and [C] were obtained in powder form.

[0519] The composition begins as a dry, weight-controlled blend of identified components with the ratios listed in each table. The dry blend is then transferred to a cylindrical injection chamber with thermal control to heat the mixture to a set process temperature. The low-melting-point A% and B% polymer materials are heated using thermal heating to allow the dispersed C% to flow into a metal mold to form an insert, without affecting or degrading the C% (pharmaceutical) which has a higher melting point and is therefore held in particulate form throughout the mixture. Once the desired process temperature is reached, a plunger or solid rod is inserted into the chamber. The outlet orifice of the heated injection chamber is physically engaged and sealed to the empty metal mold chamber. The plunger applies force to the molten material to transfer the fluidized, particulate-filled polymer mixture from the injection chamber to the metal mold chamber. Thus, the previously empty metal mold chamber is filled by the transfer of the mixture. The plunger or solid rod retracts. The injection chamber is disengaged from the metal mold. After a period of cooling to solidify the mixture, the metal mold is opened. The resulting inserts, formed in solid form according to the geometry provided by the metal mold chamber and the compositions indicated in each of the following tables, are removed from the metal mold chamber and tested.

[0520] In the table below, "rod" refers to the test results of inserts not in the receiving device, while "in the device" refers to the test results of inserts in the receiving device.

[0521] Example 2. Test protocol for therapeutic reagents

[0522] For illustrative purposes, the table below provides results of tests performed on numerous compositions in vitro using a UV scanning spectrophotometer, and of percentage “daily” releases for ocular use (e.g., approximately 12 hours to approximately 24 hours of wear), with the UV scanning spectrophotometer calibrated for the therapeutic agent to detect its concentration in 2 to 3 ml volumes of phosphate-buffered saline at pH 7. Ocular use is defined by the current FDA Class II CFR 866.5925 product definition for ocular use and scleral tissue contact indications.

[0523] To initiate testing, a UV-scan spectrophotometer concentration calibration curve was established for the therapeutic agent. Inserts were prepared according to specifications in a specific table, and a sample duration plan for the measurement duration was determined. The inserts were weighed to establish T=0. The inserts were immersed in a fixed volume of phosphate buffer. A mean body temperature of 37 °C (e.g., from approximately 36.5 °C to approximately 37.5 °C) was simulated for the confirmed intervals. At the end of each time interval, the inserts were transferred and immersed in a new phosphate buffer test container. The simulated mean body temperature of 37 °C was maintained until the next time interval. UV-scan spectrophotometer data were generated for each time interval sample. Release rate control times for the therapeutic agent were calculated, and a graphical graph of the data was generated.

[0524] Table 7

[0525] Figure 28A and 28B The graph shows data obtained from the insert in the three-component device described in Table 7, and illustrates the cumulative amounts of ciprofloxacin FB and ciprofloxacin hydrochloride released from the insert over a period of several days. The 10.23% daily release of ciprofloxacin FB (Table 7) is advantageous compared to the daily release of ciprofloxacin in the two-component EVA mixture (1.45% and 4.06%).

[0526] Table 8

[0527] Figure 29A and 29B The graph shows the data obtained from the three-component insert described in Table 8, and illustrates the cumulative amounts of ciprofloxacin FB and ciprofloxacin hydrochloride released from the insert over several days. The 82.7% daily release of dexamethasone phosphate is advantageous compared to EVA and the two-component dexamethasone mixture (3.39%, 6.14%, and 1.89%).

[0528] Table 9

[0529] Figure 30 The graph is derived from data obtained from the three-component insert described in Table 9 and shows the cumulative amount of olopatadine FB released from the insert over several days. The olopatadine release curves follow a consistent pattern and timing with the previous treatment example having similar component ratios.

[0530] Example 3. Test protocol for EVA / PEO matrix

[0531] The EVA / PEO matrix testing method follows the same sequence as the therapeutic reagent testing protocol described above, with some exceptions. For the two-component mixture, perform the EVA / PEO matrix test: A% + B% = 100%. PEO is a lubricant known for its ocular therapeutic benefits, but it cannot be detected using a UV scanning spectrophotometer. Therefore, the mass loss method is used for PEO.

[0532] The insert is manufactured according to the specifications in the matrix formulation table.

[0533] A duration-based sample plan was established for the measurements. Samples were weighed to determine T=0. Test samples were placed in fresh phosphate buffer at a fixed volume. A mean body temperature of 37°C was simulated over the confirmed time intervals. At the end of each time interval, test samples were transferred to dry containers. Inserts were patted dry and weighed to establish their hydrated mass. Inserts were air-dried for two days, then oven-dried for another day at 37°C. Inserts at "dry weight" were weighed. The release rate of the PEO component at control time was calculated, and a graphical graph was generated.

[0534] Tables 10A, 10B, 10C, and 10D are experimental summaries evaluating the release rate of the water-soluble polymer [B%] in a combination of A% (structure) + B% (erodeability) = 100%. The PEO release kinetics were investigated as a function of system variations in EVA%, PEO%, and PEO molecular weight.

[0535] Table 10A

[0536] Table 10B

[0537] Table 10C

[0538] From Table 10A, Table 10B and Table 10C and the corresponding Figure 31A , Figure 31B and Figure 31CThe illustrated kinetic study demonstrates the ability of the PEO component to drive release during the first 12 to 24 hours of insert wear.

[0539] Table 10D is a summary of the results from Tables 10A, 10B, and 10C.

[0540] Table 10D

[0541] Table 10E and corresponding Figure 31D A comparison is provided of the percentage of polyethylene oxide released during the first 12 hours for polyethylene oxide Mw 100K, 200K, and 300K with EVA 4030AC (EVA 40, meaning 40% vinyl acetate EVA block copolymer) and Polyox Mw 100K, 200K, and 300K with EVA 2816 (EVA 28, meaning 28% vinyl acetate EVA block copolymer), as the initial polyethylene oxide loading varies.

[0542] Table 10E

[0543] When combined with 40% EVA, the release rate of polyethylene oxide from the matrix reaches a lower limit of 200,000 Mw, and is rapid within the same time period when combined with 28% EVA. The data also indicate that 40% EVA-polyethylene oxide combinations with molecular weights higher than 200,000 can be released from the matrix at approximately the same general rate over a 12-hour time period, as confirmed by the 300,000 Mw data.

[0544] From a formulation perspective, feasible molecular weight ranges for 12- to 24-hour release using an EVA / PEO matrix include PEOs of 300,000 MW or lower. Additionally, blends of different PEO molecular weights less than 300,000 can serve as an additional rate control tool to adjust the erosion rate from the matrix (of the drug), a crucial tool for achieving desired therapeutic design goals in drug delivery. The ability to control drug delivery using the disclosed materials and methods is essential for precise drug delivery, which is important for many pharmaceutical products.

[0545] Example 4. Verification of ciprofloxacin FB delivery rate control using an EVA / PEO matrix

[0546] Table 10F is a summary of the matrix composition and delivery rate of ciprofloxacin FB over 7 days, with the PEO concentration of the three-component system altered. The first data (Series 1) is shown in Table 7 as part of the ciprofloxacin drug group. The last data (Series 4) is for the two-component system most similar to the two-component (EVA + drug) formulation in Table 7.

[0547] Table 10F

[0548] Tables 10D and 10F and their corresponding tables Figure 32 This study confirmed the range of drug delivery rate control that varies with changes in formulation concentration, FEO molecular weight selective blending, and the concentration of vinyl acetate EVA available from the EVA / PEO matrix system.

[0549] This disclosure is supplemented by the following references, which are incorporated herein by reference in their entirety: [1] Quaia, C; Optican, L; (2001) “Three Dimensional Rotations of the Eye” Chapter for Alder's Physiology of the Eye, 10th edition, edited by Kauffman & Alm, National Eye Institute; National Institutes of Health.

[0550] [2] Doughty MJ, Laiquzzaman M, Oblak E, Button N.; (2002) "The tear (lacrimal) meniscus height in human eyes: a useful clinical measure or anunusable variable sign?" (Cont Lens Anterior Eye. 2002 June; 25 (2): 57-65).

[0551] [3] Bekerman, I; Gottlieb, P; & Vaiman, M; (2014) "Variations in Eyeball Diameters of the Healthy Adults" (Journal of Ophthalmology, Vol. 2014, Article ID 503645, p. 5, 2014).

[0552] [4] Atchison,DJones, CESchmid,KLPritchard,NPope,JStrugnell,WRiley,R(2004)“Eye Shape in Emmetropia and Myopia”(InvestigativeOphthalmology & Visual). Science,10 / 2004, 45 / 10 / 10 / 3380-3386.

[0553] [5] Vojnikovic, B;Gabric, N;Dekaris, I;Juric, B(2013)“CurvatureAnalysis of the Corneal Front and Back Surface”(Coll.Anthropol.37(2013)Suppl.1:93-96).

[0554] [6] Hashemi,H,Khabazkhoob,M; Emamian,MH; Shariati,M;Yekta,A;Photouhi,A; “White to white corneal diameter distribution in an adultpopulation”(Journal of Current Ophthalmology 27(2015)21 -24).

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[0574] The full teachings of any patents, publications, and references cited herein are incorporated herein by reference.

[0575] While exemplary embodiments have been specifically shown and described, those skilled in the art will understand that various changes in form and detail may be made therein, within the scope of the embodiments covered by the appended claims.

Claims

1. An eye-receiving device placed under the eyelid, the eye-receiving device comprising: At least three plates, wherein at least one plate includes a rear surface having at least one protrusion having a contact surface that contacts the sclera of the eye and provides offset space between the sclera and the rear surface of the at least one plate, and the at least one plate is connected to an elongated support member made of a flexible material, the elongated support member including a first end and a second end.

2. The receiving device according to claim 1, wherein, The at least one plate is connected to the first end of the elongated support member, and a plate is connected to the second end of the elongated support member.

3. The receiving device according to claim 1 or 2, wherein, A flexible connector connects the at least one plate to the elongated support member.

4. The receiving device according to claim 3, wherein, The connection between the flexible connector and the elongated support member is configured to be positioned adjacent to the corner of the eye when the eye-connecting device is under the eyelid.

5. The receiving device according to claim 1 or 2, wherein, The contact surface forms a boundary surrounding the offset space.

6. The receiving device according to claim 1 or 2, wherein, The at least one protrusion is a complete annular band.

7. The receiving device according to claim 1 or 2, wherein, The at least one protrusion is annular.

8. The receiving device according to claim 1 or 2, wherein, The posterior surface has at least three protrusions, each protrusion having a contact surface that contacts the sclera of the eye and provides the offset space between the sclera and the posterior surface of the at least one plate.

9. The receiving device according to claim 1 or 2, wherein, The contact surface is a convex contact surface.

10. The receiving device according to claim 1 or 2, wherein, The at least one plate further includes a front surface on the other side of the at least one plate opposite to the rear surface, the front surface having at least one protrusion having a contact surface that contacts the sclera of the eye and provides offset space between the sclera and the front surface of the at least one plate.

11. The receiving device according to claim 10, wherein, The contact surface of the at least one protrusion on the front surface is a convex contact surface.

12. The receiving device according to claim 1 or 2, wherein, The periphery of one or more of the at least three plates is curved.

13. The receiving device according to claim 1 or 2, wherein, One or more of the at least three plates extend laterally from the elongated support member.

14. The receiving device according to claim 1 or 2, wherein, The length of the slender support member is between 3 mm and 24 mm.

15. The receiving device according to claim 1 or 2, wherein, The length of the slender support member is between 3 mm and 8 mm.

16. The receiving device according to claim 1 or 2, wherein, The length of the slender support member is between 4 mm and 10 mm.

17. The receiving device according to claim 1 or 2, wherein, The length of the slender support member is between 6 mm and 16 mm.

18. The receiving device according to claim 2, wherein, The elongated support member, the at least one plate connected to the first end near the elongated support member, and the plate connected to the second end near the elongated support member are substantially coplanar, flexibly interconnected, and configured to be adapted to irregular surfaces.

19. The receiving device according to claim 1 or 2, wherein, One or more of the at least three plates are connected to the elongated support member between the first end and the second end of the elongated support member, and the one or more plates are substantially coplanar with the elongated support member.

20. The receiving device according to claim 1 or 2, wherein, Each plate is connected to the slender support member via a flexible connector.

21. The receiving device according to claim 1 or 2, wherein the receiving device comprises at least four plates, wherein, At least two plates are connected to the elongated support member via bent flexible connectors, and at least two other plates are connected to the elongated support member via substantially straight flexible connectors.

22. The receiving device according to claim 1 or 2, wherein, The thickness of one or more of the at least three plates decreases from front to back as the distance from the center region of the receiving device increases.

23. The receiving device according to claim 1 or 2, wherein, Each plate is connected to the same side of the elongated support member.

24. The receiving device according to claim 1 or 2, wherein, The slender support member is curved.

25. The receiving device according to claim 24, wherein, The slender support member has a smoothly curved outer surface.

26. The receiving device according to claim 1 or 2, wherein, One or more of the at least three plates are generally circular.

27. The receiving device according to claim 1 or 2, wherein, The widest portion of the rear surface of the at least one plate is 2 mm to 7 mm.

28. The receiving device according to claim 26, wherein, The diameter of the generally circular one or more plates is 2 mm to 7 mm.

29. The receiving device according to claim 1 or 2, wherein, The slender support member has an arched portion and an outer gentle slope portion, each of which extends from the arched portion.

30. The receiving device according to claim 29, wherein, The arch portion has a radius of curvature between 0.0 mm and 6.0 mm.

31. The receiving device according to claim 29, wherein, The arch portion is a segment of arch located in the central region of the receiving device between the first and second ends of the elongated support member.

32. The eye-viewing device according to claim 1 or 2, the eye-viewing device further comprising a substance to be delivered to the eye in one or more of the at least three plates.

33. The receiving device according to claim 1 or 2, wherein, One or more of the at least three plates provide at least one recess for holding the material to be delivered to the eye.

34. The receiving device according to claim 33, wherein, The at least one recess is cylindrical.

35. The eye-viewing device according to claim 33, further comprising the substance to be delivered to the eye in the at least one recess.

36. The receiving device according to claim 33, wherein, The at least one recess includes an opening configured to receive the substance to be delivered to the eye.

37. The receiving device according to claim 33, wherein, An insert is present in at least one recess, and wherein the insert is configured to contain the substance to be delivered to the eye.

38. The receiving device according to claim 37, wherein, The receiving device further includes a retaining element for holding the insert in the at least one recess.

39. The receiving device according to claim 38, wherein, The retaining element is a sealing diaphragm that is attached to the contact device, the insert, or both the contact device and the insert.

40. The receiving device according to claim 39, wherein, The sealing diaphragm includes at least one pore.

41. The receiving device according to claim 38, wherein, The retaining element includes a lip at the opening of the at least one recess.

42. The receiving device according to claim 36, wherein, The opening is generally polygonal.

43. The receiving device according to claim 36, wherein, The opening is generally hexagonal.

44. The eye-contact device of claim 37, further comprising orifices in the one or more plates, the eye-contact device being configured to dispense the substance from the insert through the orifices into the eye to provide a bidirectional drug delivery system.

45. The receiving device according to claim 1 or 2, wherein, At least a portion of the receiving device is formed of a polymer material.

46. ​​The receiving device according to claim 37, wherein, The insert comprises a composition containing a pharmaceutically active agent and a pharmaceutically acceptable carrier.

47. The receiving device according to claim 46, wherein, Pharmaceutically acceptable carriers include water-soluble polymers.

48. The receiving device according to claim 46, wherein, Pharmaceutically acceptable carriers include water-insoluble polymers.

49. An eye-viewing device placed under the eyelid, the eye-viewing device comprising: Slender support components made of flexible materials; as well as At least three plates, wherein at least one plate is connected to the elongated support member, the at least one plate including a rear surface having at least one protrusion having a contact surface that contacts the sclera of the eye and provides offset space between the sclera and the rear surface of the at least one plate.

50. The receiving device according to claim 49, wherein, The contact surface is convex.

51. The receiving device according to claim 49 or 50, wherein, The slender support member and the at least one plate are substantially coplanar.

52. The receiving device according to claim 49 or 50, wherein, The at least one plate is connected to the elongated support member near its end.

53. The receiving device according to claim 49 or 50, wherein, The first plate is connected to one end of the elongated support member and the second plate is connected to the elongated support member to the other end of the elongated support member, the elongated support member, the first plate and the second plate being substantially coplanar.

54. An eye-contact device placed under the eyelid to deliver material to the eye, the eye-contact device comprising: Slender support components; At least three plates, wherein a first plate is connected near one end of the elongated support member and a second plate is connected near the other end of the elongated support member, wherein the first plate and the second plate are substantially coplanar with the elongated support member; and Both the first plate and the second plate include a rear surface, each rear surface having at least one protrusion having a contact surface that contacts the sclera of the eye and provides offset space between the sclera and the rear surface.

55. The receiving device according to claim 54, wherein, At least one contact surface is convex.

56. The receiving device according to claim 54 or 55, wherein, The receiving device also contains a pharmaceutical active agent.

57. The receiving device according to claim 56, wherein, The active pharmaceutical ingredient is disposed within at least one of the at least three plates.

58. The receiving device according to claim 54 or 55, wherein, At least a portion of the contact device is formed from a pharmaceutically active agent blended with other materials.

59. The receiving device according to claim 54 or 55, wherein, At least one of the at least three plates provides a cavity capable of receiving a pharmaceutical active agent.

60. The eye-receiving device according to claim 59, wherein the eye-receiving device further comprises the pharmaceutical active agent in the recess.

61. The eye-connecting device according to claim 59, further comprising a removable insert in the recess, wherein, The insert can contain the pharmaceutical active agent.

62. The eyepiece receiving device according to claim 61, further comprising a retaining element for retaining the insert in the recess.

63. An eye-receiving device placed under the eyelid of the eye, the eye-receiving device comprising: Slender support components; At least three plates, wherein at least one plate is connected to the elongated support member, and the at least one plate includes: (i) a scleral contact surface having at least three points configured to contact the sclera of the eye; and (ii) a remote surface configured to hold the sclera remote from the eye by the at least three points, the remote surface and the at least three points providing offset space configured to hold tears.

64. The eye-viewing device according to claim 63, further comprising a pharmaceutically active agent for delivery to the eye.

65. The receiving device according to claim 64, wherein, When the eye-connecting device is placed under the eyelid, the active pharmaceutical ingredient is delivered to the eye via tears.

66. The receiving device according to any one of claims 63 to 65, wherein, The surface area of ​​the scleral contact surface is less than 20% of the surface area of ​​the surface furthest away from the sclera.

67. The receiving device according to any one of claims 63 to 65, wherein, The contact device is flexible and adapted to the scleral contact surface.

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