Eyelets

Abstract

The present invention relates to a sustained release intraocular drug delivery device comprising an elongate body, two sealed ends, and an eyelet fixedly connected to at least one of the ends, the elongate body further comprising a polymer matrix core intermixed with at least one therapeutic agent, and a polymer coating completely surrounding the polymer matrix material, the eyelet being configured to assist in withdrawal of the device.

Description

[Technical field]

[0001] The present invention relates to sustained release drug delivery devices / implants, in particular to removable sustained release drug delivery devices / implants intended for the long-term and controlled release of one or more therapeutic agents, and more particularly to sustained release drug delivery devices / implants configured to be beneficial for removal procedures. [Background technology]

[0002] A variety of ophthalmic and non-ophthalmic diseases require the administration of a variety of drugs to the eye. Although eye drops and gels are effective drug delivery vehicles, they also have significant drawbacks. Specifically, eye drops mix with the tears in the tear film, but their residence time in the tear film may only be 2-5 minutes. Only 5% of the drug can be absorbed locally; some or all of the remainder is transported from the lacrimal sac to the lacrimal duct and eventually absorbed into the bloodstream. Absorption into the bloodstream has at least two adverse effects; first, most of the drug is wasted, and second, the presence of the drug in the bloodstream may have harmful side effects in other parts of the body. Gels may adhere to the eye more effectively, but they may also blur the patient's vision for an extended period of time. Both eye drops and gels require frequent reapplication for some treatments. Thus, there remains a need for improved methods of drug delivery to the eye that do not drain from the targeted location or require frequent administration.

[0003] Considering the shortcomings of eye drops, it is understandable that various alternatives have been proposed. Known alternatives to eye drops include the placement of drug-containing or impregnated structures under the eyelid. Such solid ocular dosage forms appear to have significant potential advantages compared to eye drop-based ocular drug treatments. In particular, ocular drug delivery implants may help overcome poor patient compliance, the difficulty and frequent misapplication of traditional eye drops and other dosage forms, as well as the limited effective drug absorption from eye drops, and at the same time, may facilitate the advantageous application of advances in polymer chemistry and the introduction of the concept of sustained / controlled drug release from other known drug delivery devices / implants.

[0004] As an approach to circumvent the drawbacks of focal topical delivery, local ocular treatment routes have been attempted in which drugs are injected directly into the vitreous through the sclera (i.e., the spherical, collagen-rich outer covering of the eyeball). However, intravitreal injections tend not to provide sustained release due to short half-lives and rapid drug clearance. As a result, monthly injections are often required to maintain therapeutic ocular drug concentrations, which is not practical for many patients, especially in the treatment of degenerative or persistent diseases. Furthermore, monthly intravitreal injections are not without risk, as several undesirable effects associated with repeated injections can occur, including subconjunctival hemorrhage, intraocular infection, exacerbation of existing cataracts, incidental lesions to the lens, and / or retinal detachment.

[0005] Implantable intraocular sustained release delivery devices / implants have the potential to avoid the drawbacks and complications that may arise from both systemic and local therapies (i.e., topical administration or intravitreal injection). However, despite the fact that various intraocular implant devices / implants have been described and used in the art, the full potential of this therapeutic route has not been achieved.

[0006] In view of the above, there remains a need in the art for improved non-degradable sustained release intraocular drug delivery devices that are simple to manufacture, can release therapeutic agents at a sustained and controlled rate over an extended period of time, and are easily removable. We note that while some biodegradable implants exist, these typically last less than a year before completely degrading, which is undesirable.

[0007] The placement of such devices is often assisted by an injection device. US Patent Application Publication Nos. 2019 / 083313 and 2019 / 091012 disclose exemplary devices and methods for controlling the placement of an intraocular implant in a patient's eye. The removal of such devices is often accomplished by the same injection device, which removes the drug delivery device by picking up the body with, for example, a hook-like pick-up structure at the end of the injection device.

[0008] EP 3068372 discloses a sustained release intraocular drug delivery device comprising: (a) a polymer matrix core mixed with at least one therapeutic agent; and (b) a polymer coating completely surrounding said polymer matrix material, where the degree of crosslinking of the polymer selected for the polymer coating controls the drug release rate from the intraocular drug device. In certain embodiments, the drug delivery device has tags or protrusions to facilitate manipulation during insertion or removal of said device. However, it is not explicitly disclosed how the protrusions aid in the insertion or removal process. The technical features of said protrusions remain unclear.

[0009] WO2010141729 discloses a therapeutic system with an ocular insert that is placed in an area outside the optical zone of the eye. The ocular insert includes two structures: a first skeletal structure and a second cushion structure. However, this device does not produce a sustained release of a therapeutic agent. The first structure requires that the second structure be ring-shaped and does not aid in withdrawal of the device.

[0010] One of the current goals in designing a non-degradable sustained intraocular drug delivery device is that i) the device should be easily withdrawn; ii) it should not interfere with the placement of the drug delivery device; and iii) it should be easy to manufacture given the complexities of manufacturing micro-sized parts.

[0011] Applicant notes that the above problems are particularly problematic when the device itself is thinner and therefore more fragile, which is desirable because it causes much less patient interference (both reduced line of sight and ocular discomfort) and allows for more efficient delivery of therapeutic agents.

[0012] A further problem is linearization, ie, being able to fold the device for placement in a compact (very narrow) configuration by a simple surgical procedure, which is also addressed by the current invention.

[0013] Therefore, it is necessary to design certain features into the sustained intraocular drug delivery device to solve one or more of the above problems, and it should be noted that such features should not cause further problems such as affecting sustained release, resulting in an unpleasant use experience, etc. Summary of the Invention [Problem to be solved by the invention]

[0014] It is therefore an object of the present application to provide an improved sustained release intraocular drug delivery device that overcomes at least some of the above problems.

[0015] The inventors have designed an insoluble, inert, sustained release intraocular drug delivery device for insertion into the posterior chamber of the eye (more specifically, the sulcus). Since the insertion of the device into the sulcus does not initiate the fibrotic process and is inactive in ocular fluids, the device can be removed after the drug is exhausted, or in case of undesirable side effects to the drug, or at an earlier stage according to a determined scheme. Furthermore, the use of the sulcus as the insertion site allows the dimensions of the device to be such that it can achieve sustained release of the selected therapeutic agent for up to five years. The invention also includes an eyelet configured to assist in withdrawal of the device. Furthermore, the inventors have found a convenient method of manufacturing said intraocular device, allowing standard manufacturing techniques to achieve uniformity of the product.

[0016] The present invention provides in a first aspect a sustained release intraocular drug delivery device comprising an elongate body, two (sealed) ends and an eyelet fixedly connected to at least one of the ends, The elongate body further comprises a polymer matrix core having at least one therapeutic agent admixed therewith and a polymer coating completely surrounding the polymer matrix material, and the eyelet is configured to assist in withdrawal of the device, providing a sustained release intraocular drug delivery device that is essentially free of the (and any other) therapeutic agent.

[0017] In this manner, the inventors have achieved a sustained release intraocular drug delivery device with an eyelet configured to aid in withdrawal of the device. [Brief description of the drawings]

[0018] [Figure 1] Fig. 1A shows a perspective view of a sustained release intraocular drug delivery device according to an embodiment of the present application, together with a first preferred embodiment of an eyelet, and Fig. 1B shows a perspective view of dimensional details of the embodiment of Fig. 1A. [Diagram 2]2A is a schematic diagram showing a perspective view of a sustained release intraocular drug delivery device according to an embodiment of the present application having a second preferred embodiment of an eyelet, and FIG 2B is a schematic diagram showing a perspective view of dimensional details of the embodiment of FIG 2A. [Diagram 3] 3A is a schematic diagram showing a perspective view of a sustained release intraocular drug delivery device according to an embodiment of the present application having a third preferred embodiment of an eyelet, and FIG. 3B is a schematic diagram showing a perspective view of dimensional details of the embodiment of FIG. 3A. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0019] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.

[0020] As used herein, the singular forms "a," "an," and "the" include both singular and plural references unless the context clearly dictates otherwise. As used herein, the terms "comprising," "comprises," and "comprised of" are synonymous with "including," "includes," or "containing," and are inclusive or open-ended and do not exclude additional, unmentioned members, elements, or method steps. The terms "comprising," "comprises," and "comprised of" also include the term "consisting of."

[0021] The recitation of numerical ranges by endpoints includes all values ​​and fractions within each range, as well as the recited endpoints. When numerical values ​​are used, the numerical values ​​include not only the exact numerical values, but also all numerical values ​​that are rounded up to the exact numerical value according to standard mathematical and / or statistical rules. For example, an annular segment of a "180 degree" ring includes angles of 179 degrees and 181 degrees, more specifically 179.5 degrees; 179.6 degrees; 179.7 degrees; 179.8 degrees; 179.9 degrees; 180.0 degrees; 180.1 degrees; 180.2 degrees; 180.3 degrees; 180.4 degrees. When used in conjunction with the term "about," the annular segment of the ring also includes angles that vary from the exact angle by as much as 0.1 degrees, 0.2 degrees, 0.3 degrees, 0.4 degrees, 0.5 degrees, 0.6 degrees, 0.7 degrees, 0.9 degrees, or 1.0 degrees. Those skilled in the art will appreciate that the same principles apply when the dimensions of a sustained release intraocular drug delivery device are expressed in units of length; for example, a length of "14.0 mm" encompasses length values ​​between 13 and 15 mm, more specifically 13.5; 13.6; 13.7; 13.8; 13.9; 14.0; 14.1; 14.2; 14.3; and 14.4 mm. Thus, the term "about 14.0 mm" encompasses lengths that vary from said exact length by as much as 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.7, 0.9, or 1.0 mm.

[0022] Similarly, when a period of time is indicated using a numerical value such as "about 30 minutes," the numerical value encompasses not only the exact time indicated, but also periods that deviate therefrom, for example, by less than 1 minute, 30 seconds, or by 1, 2, 3, 4, or 5 minutes, etc. Similarly, the term "about 30 seconds" encompasses from about 20 seconds, 25 seconds to about 35 seconds, 40 seconds, and any time in between.

[0023] As used throughout this disclosure, the terms "concentration" and "content" are used interchangeably and refer to the weight concentration or mass fraction of a component, i.e., the mass of a component divided by the total mass of all components, and are expressed as % by weight or % w / w.

[0024] The term "about" as used herein when referring to measurable values ​​such as parameters, amounts, and time durations is meant to encompass variations of the stated value of no more than + / -10%, preferably no more than + / -5%, more preferably no more than + / -1%, and even more preferably no more than + / -0.1%, to the extent appropriate for practice with the disclosed invention. It is to be understood that the values ​​to which the modifier "about" refers are themselves specifically disclosed, and preferably disclosed.

[0025] References throughout this specification to "one embodiment" or "an embodiment" mean that a particular feature, structure, or characteristic described in connection with an embodiment is included in at least one embodiment of the present application. Thus, the appearances of the phrases "in one embodiment" or "in an embodiment" in various places throughout this specification do not necessarily all refer to the same embodiment, but may. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner, as would be apparent to one of ordinary skill in the art from this disclosure, in one or more embodiments.

[0026] As a further guide, definitions of terms used herein are included to better understand the teachings of the present application.

[0027] The sustained release intraocular drug delivery device of the present invention is defined in the claims.

[0028] Preferably, the device includes or is formed from a compliant annular segment configured for the sulcus of the eye. More specifically, the device has a cross-sectional diameter in the range of 0.10-0.80 mm. The annular segment can range from 90° to 360° of the ring. Preferably, the annular segment ranges from 180° to 360° of the ring, more preferably from 300° to 360°. In this preferred configuration, the eyelet is attached to the elongated body of the device at two attachment points, and the two attachment points (4, 5) seal the two ends of the elongated body of the device so that the device forms a 360° ring even if the elongated body is too short to form a 360° ring. The annular segment can have an outer or outer diameter in the range of 5.0-15.0 mm, preferably 7.5-15.0 mm, more preferably 9.0-14.0 mm, or 10.0-12.0 mm, for example about 11.0 mm. As used herein, the "outer diameter" or "outside diameter" of an annular body or annular segment means the diameter of the circumscribing circle of the annular body or annular segment.

[0029] "Sustained release" dosage forms are designed to control the release of a drug over a specific period of time.

[0030] As used herein, the term "therapeutic agent" or "compound" is used interchangeably with "drug" and refers to a chemical substance used to treat, cure, prevent, or diagnose a disease. Examples of such therapeutic agents include, but are not limited to, antiangiogenic compounds such as bevacizumab, ranibizumab, aflibercept, borolanib, sunitinib (maleate) and axitinib, beta-blockers such as timolol (maleate), prostaglandin analogs such as latanoprost, bimatoprost, travoprost, latanoprost bunod, tafluprost and omidenepagisopropyl, carbonic anhydrase inhibitors such as dorzolamide (hydrochloride) and brinzolamide, alpha-2 adrenergic agonists such as brimonidine (tartrate), Rh antagonists such as netarsuldil mesylate and ripasudil. o-kinase inhibitors, corticosteroids such as triamcinolone, dexamethasone, difluprednate, loteprednol etabonate, fluorometholone, hydrocortisone and acetonide fluocinolone, NSAIDs such as nepafenac, bromfenac, diclofenac, ketorolac, indomethacin and pranoprofen, antibiotics such as moxifloxacin, tobramycin, levofloxacin, gatifloxacin, ofloxacin, besifloxacin, erythromycin, gentamicin, chloramphenicol, azithromycin, polymyxin B sulfate and bacitracin or cyclosporine. Thus, a general list may include: anti-glaucoma agents (i.e. prostaglandin analogues, carbonic anhydrase inhibitors, alpha 2 adrenergic receptors, beta blockers, Rho kinase inhibitors), anti-inflammatory agents, anti-angiogenic compounds, and / or immune system modulating agents.

[0031] As used herein, an "intraocular drug delivery device" refers to a device that is structured, sized, or otherwise configured to be placed in the eye; once placed, it locally releases a selected drug. The intraocular drug delivery device according to the present application may be biocompatible with the physiological conditions of the eye and does not cause side effects in normal and / or pseudophakic eyes. The intraocular drug delivery device according to the present application may be placed in the eye without disturbing the vision of the eye.

[0032] As used herein, a "pseudophakic eye" refers to an eye that has been implanted with an intraocular lens. The intraocular lens can replace a lens that has been damaged, for example due to a perforated wound or ulcer; or a lens that does not function properly, for example in the case of cataracts or myopia. An intraocular lens can also be implanted in patients who lack a lens due to a congenital abnormality.

[0033] The "matrix core" of the sustained release intraocular drug delivery device of the present application is located at the innermost part of the device. It comprises one or more materials that are insoluble and inert (i.e., biocompatible) in ocular fluids, and at the same time are not absorbed or degraded by ocular tissues. The use of materials that dissolve quickly or are highly soluble in ocular fluids must be avoided, as dissolution of the wall will not only affect the consistency of drug release, but also the ability of the device to remain in place for an extended period of time. Preferred materials for use in the matrix core of the sustained release intraocular drug delivery device of the present application include, for example, polymers.

[0034] The matrix core of the sustained release intraocular drug delivery device of the present invention is characterized in that a therapeutic agent is dispersed or distributed therein, i.e., at least one therapeutic agent is mixed into the matrix core, preferably a polymeric matrix core. Dispersion of a therapeutic agent into the matrix core can be achieved, for example, by crosslinking a blend of a crosslinkable polymer (e.g., PDMS) and at least one therapeutic agent, or by extrusion of a thermoplastic polymer (e.g., EVA, PE, PMMA) and at least one therapeutic agent.

[0035] The matrix core of the present sustained release intraocular drug delivery device is made of a polymer.

[0036] As used herein, the term "polymer" refers to a molecule having a structure composed of multiple repeating units. Thus, a "biocompatible polymer" is a polymer that is tolerated by living organisms. It may be of natural or synthetic origin.

[0037] The materials used in the intraocular drug delivery device of the present invention are specifically selected to ensure that the device forms a compliant annular segment, i.e., the annular segment can be straightened by the application of force, but returns to its original annular shape when the force is removed. This is important because the temporary straightening allows for easy insertion of the device into the eye, and then the device returns to its original shape after insertion, conforming to the anatomy of the sulcus of the eye. The specific dimensions of the present sustained release intraocular drug delivery device facilitate its insertion into the eye and its removal after use.

[0038] A variety of polymers can be used to form the polymer matrix core having at least one therapeutic agent dispersed therein. Preferably, the polymer is chemically compatible with and permeable to the therapeutic agent.

[0039] In certain embodiments, the polymer matrix core is made of ethylene-co-vinyl acetate (EVA), poly(dimethylsiloxane) (PDMS), polypropylene (PP), polyethylene (PE), (plasticized) polyethylene terephthalate (PET), polymethylmethacrylate (PMMA), polyvinyl acetate, crosslinked polyvinyl alcohol, crosslinked polyvinyl butyrate, ethylene-ethyl acrylate copolymers, polyethylhexyl acrylate, polyvinyl alcohol, polyvinyl ester, polyvinyl butyrate, polyamide, polybutyl methacrylate, plasticized nylon, plasticized soft The polymer may comprise a polymer selected from the group consisting of: nylon, polyisoprene, crosslinked polyvinylpyrrolidone, poly(1,4-isopropylidenediphenylene carbonate), silicone rubber, ethylene propylene rubber, silicone carbonate copolymer, polycarbonate, polyurethane (preferably thermoplastic), thermoplastic elastomer (TPE) (e.g., SEBS (styrene-ethylene-butylene-styrene), SBS (styrene-butadiene-styrene), MBM (methyl methacrylate-butadiene-methyl methacrylate), polyolefin, or a combination thereof.

[0040] In certain embodiments, the polymer matrix core comprises a polymer selected from the group consisting of ethylene-co-vinyl acetate (EVA), poly(dimethylsiloxane) (PDMS), polypropylene, polyethylene), polymethylmethacrylate (PMMA), polyurethane (preferably thermoplastic), and cross-linked polyvinyl alcohol, or combinations thereof, and at least one therapeutic agent is dispersed throughout the polymer (i.e., at least one therapeutic agent is mixed with the polymer).

[0041] The polymer matrix core of the sustained release intraocular drug delivery device of the present invention also contains at least one (but potentially two or more) therapeutic agent. The polymer matrix core of the sustained release intraocular drug delivery device of the present invention may contain 0.1-50 wt% of the at least one therapeutic agent, based on the total weight of the polymer matrix material. Preferably, the polymer matrix core contains 1.0-50 wt% or 5.0-50 wt% of said at least one therapeutic agent, based on the total weight of the polymer matrix material.

[0042] The matrix core or polymer matrix core or sustained release intraocular drug delivery device of the present invention may have a support structure to increase the flexibility of the device. Preferably, the support structure is a filament. More preferably, the structure is a metal filament.

[0043] In some embodiments, the matrix core or polymer matrix core of the sustained release intraocular drug delivery device of the present application comprises metal filaments.

[0044] The sustained release intraocular drug delivery device of the present application also includes a "polymeric coating" that completely surrounds the matrix material, which further regulates the release of the therapeutic agent contained within the polymeric matrix material. The polymeric coating includes a polymer that is insoluble and inert in ocular fluids (i.e., biocompatible) while at the same time not being absorbed or degraded by ocular tissues. Preferably, the polymer of the polymeric coating is permeable to the therapeutic agent.

[0045] In certain embodiments, the polymer coating comprises one or more polymers selected from the group consisting of ethylene-co-vinyl acetate (EVA), poly(dimethylsiloxane) (PDMS), polypropylene (PP), polyethylene (PE), (plasticized) polyethylene terephthalate, polymethylmethacrylate (PMMA), cross-linked polyvinyl alcohol, polyolefins; regenerated, insoluble, non-erodible cellulose, acylated cellulose, esterified cellulose, cellulose acetate propionate, cellulose acetate butyrate, cellulose acetate phthalate, cellulose acetate diethyl-aminoacetate; polyurethanes (preferably thermoplastic), polycarbonates, and microporous polymers formed by co-precipitation of polycations and polyanion-modified insoluble collagen, or combinations thereof.

[0046] In certain embodiments, the coating comprises a polymer selected from the group consisting of ethylene-co-vinyl acetate (EVA), poly(dimethylsiloxane) (PDMS), polypropylene, polyethylene, polymethylmethacrylate (PMMA), polyurethane (preferably thermoplastic), and cross-linked polyvinyl alcohol, or combinations thereof.

[0047] In certain embodiments, the sustained release intraocular drug delivery device comprises: a) a matrix core comprising a polymer selected from the group consisting of ethylene-co-vinyl acetate (EVA), poly(dimethylsiloxane) (PDMS), polypropylene, polyethylene, polymethylmethacrylate (PMMA), polyurethane (preferably thermoplastic), and cross-linked polyvinyl alcohol, or combinations thereof, wherein at least one therapeutic agent, preferably timolol, is mixed with the polymer; b) a coating comprising a polymer selected from the group consisting of ethylene-co-vinyl acetate (EVA), poly(dimethylsiloxane) (PDMS), polypropylene, polymethylmethacrylate (PMMA), polyurethane (preferably thermoplastic), and cross-linked polyvinyl alcohol, or combinations thereof.

[0048] In certain embodiments, the sustained release intraocular drug delivery device comprises: (a) a matrix core comprising polyethylene (PE), wherein at least one therapeutic agent, preferably timolol, is mixed with the PE; (b) a coating comprising polyethylene (PE).

[0049] In certain embodiments, the sustained release intraocular drug delivery device comprises: (a) a matrix core comprising polyethylene (PE), wherein at least one therapeutic agent, preferably timolol, is mixed with the PE; (b) a coating comprising polymethylmethacrylate (PMMA).

[0050] In certain embodiments, the sustained release intraocular drug delivery device comprises: (a) a matrix core comprising polymethylmethacrylate (PMMA), wherein at least one therapeutic agent, preferably timolol, is mixed with the PMMA; (b) a coating comprising polymethylmethacrylate (PMMA).

[0051] In certain embodiments, the sustained release intraocular drug delivery device comprises: (a) a matrix core comprising polymethylmethacrylate (PMMA), wherein at least one therapeutic agent, preferably timolol, is mixed with the PMMA; (b) a coating comprising polyethylene (PE).

[0052] In certain embodiments, the sustained release intraocular drug delivery device comprises: (a) a matrix core comprising polymethylmethacrylate (PMMA), wherein at least one therapeutic agent, preferably timolol, is mixed with the PMMA; (b) a coating comprising ethylene-co-vinyl acetate (EVA).

[0053] In certain embodiments, the sustained release intraocular drug delivery device comprises: (a) a matrix core comprising polyethylene (PE), wherein at least one therapeutic agent, preferably timolol, is mixed with the PE; (b) a coating comprising ethylene-co-vinyl acetate (EVA).

[0054] In certain embodiments, the sustained release intraocular drug delivery device comprises: (a) a matrix core comprising polymethylmethacrylate (PMMA), wherein at least one therapeutic agent, preferably timolol, is admixed with the PMMA; (b) a coating comprising polypropylene (PP).

[0055] In certain embodiments, the sustained release intraocular drug delivery device comprises: a) a matrix core comprising ethylene-co-vinyl acetate (EVA), wherein at least one therapeutic agent, preferably timolol, is mixed with the EVA; (b) a coating comprising polyethylene (PE).

[0056] In certain embodiments, the sustained release intraocular drug delivery device comprises: a) a matrix core comprising ethylene-co-vinyl acetate (EVA), wherein at least one therapeutic agent, preferably timolol, is mixed with the EVA; (b) a coating comprising polymethylmethacrylate (PMMA).

[0057] In certain embodiments, the sustained release intraocular drug delivery device comprises: a) a matrix core comprising ethylene-co-vinyl acetate (EVA), wherein at least one therapeutic agent, preferably timolol, is mixed with the EVA; b) a coating comprising ethylene-co-vinyl acetate (EVA).

[0058] In certain embodiments, the sustained release intraocular drug delivery device comprises: a) a matrix core comprising ethylene-co-vinyl acetate (EVA), wherein at least one therapeutic agent, preferably timolol, is mixed with the EVA; b) a coating comprising polyurethane (PU).

[0059] In certain embodiments, the sustained release intraocular drug delivery device comprises: a) a matrix core comprising polyurethane (PU), wherein at least one therapeutic agent, preferably timolol, is mixed with the PU; b) a coating comprising ethylene-co-vinyl acetate (EVA).

[0060] In certain embodiments, the sustained release intraocular drug delivery device comprises: a) a matrix core comprising polyurethane (PU), wherein at least one therapeutic agent, preferably timolol, is mixed with the PU; b) a coating comprising polyurethane (PU).

[0061] Further details of the elongate body of the sustained release intraocular drug delivery device are described in EP 3068372. That is, the technical details regarding the dimensions, composition, materials and manufacturing process of the elongate body of the sustained release intraocular drug delivery device herein are in accordance with the disclosure of EP 3068372.

[0062] This specification focuses on the design of islets for inclusion in sustained release intraocular drug delivery devices.

[0063] The present invention relates to a sustained release intraocular drug delivery device comprising: an elongate body, two (sealed) ends, and an eyelet fixedly connected to at least one end, said body further comprising a polymer matrix core intermixed with at least one therapeutic agent, and a polymer coating completely surrounding said polymer matrix material, said eyelet being configured to assist in withdrawal of said device.

[0064] The eyelet, and preferably the ends, do not contain a therapeutic agent. The two (sealed) ends and the eyelet are made of at least one polymer that is compatible with the polymer contained in the sustained release intraocular drug delivery device. The polymer can be a core polymer, a coating polymer or another polymer. There is no chemical reaction between the materials of the eyelet, the two (sealed) ends and the sustained release intraocular drug delivery device body.

[0065] In the present invention, the eyelet preferably comprises at least a connecting portion and a gripping portion, the gripping portion preferably including an opening therethrough, the connecting portion connecting the eyelet to at least one, preferably both, of the (sealed) ends, and the gripping means extending therefrom away from the body of the device and adapted to be manipulated by the user for removal (and possibly for positioning within the eye).

[0066] In a preferred embodiment, the eyelet includes a constriction, said constriction being contained within the connecting portion or located between the gripping portion and the connecting portion, said constriction allowing the eyelet to be folded against the ring body for straightening. In a further preferred embodiment, said constriction has a minimum cross-sectional dimension smaller than a cross-sectional dimension of the body, preferably smaller than a cross-sectional dimension of the gripping portion.

[0067] In a particularly preferred embodiment, the smallest cross-sectional dimension is along a direction essentially perpendicular to the eyelet opening (the direction of a line extending through the opening). However, the smallest width of the constriction (in the plane in which the opening lies) is also preferably at most equal to (or narrower than) the cross-sectional dimension of the elongate body. Most preferably, said smallest width and smallest cross-sectional dimension of the constriction are present in the overlapping portion of said constrictions. Said reduction in dimension further simplifies the folding of the eyelet.

[0068] In fact, preferably, the device is folded before application to the patient to avoid large incisions, such that the device is folded to a generally straight shape, such folding being accomplished by gentle longitudinal compression.

[0069] In other words, preferably in the context of the present invention, the words "compress", "straighten" and "fold" refer to the same action, which allows for easy surgical placement in a compact (very narrow) configuration.

[0070] In a preferred embodiment, the gripping portion has at least approximately the same width, and preferably a wider overall width, at the location of the opening compared to the location where said gripping portion joins the joining portion in order to improve straightening.

[0071] In certain embodiments, the elongate body has a maximum cross-sectional diameter of 0.8 mm, preferably no more than 0.7 mm, 0.6 mm, or 0.5 mm. In the most preferred embodiments, the elongate body has a cross-sectional diameter of 0.2 mm to 0.4 mm, such as about 0.30 mm to 0.35 mm, or about 0.25 mm to 0.30 mm. This much thinner configuration is notably different from the prior art in that it is more fragile and may break during direct handling of the device (which may leave exposed drug-laden polymer matrix material in the eye), while the thinness generally makes handling more difficult, further increasing the need for eyelets to withdraw the device.

[0072] In certain embodiments, the eyelet extends from the elongated body for at least 1.0 mm, preferably at least 1.25 mm, more preferably at least 1.5 mm, and even more preferably at least 1.7 mm, 1.8 mm, 1.9 mm, 2.0 mm, or (about) 2.1 mm, ensuring both a suitable length for easy pick-up during withdrawal of the device without potentially damaging the elongated body. Furthermore, it is important that the eyelet is visible under pupil dilation while not interfering with the vision of the eye, which is achieved by the minimum distance set out above. Note that, as can be seen in the figure, this is mainly (more than 80%) about the length of the so-called gripping part.

[0073] Conversely, applicants have indicated that the maximum length of the eyelet extending from the elongate body should preferably be set at about 4.5 mm, preferably about 4.0 mm, more preferably about 3.5 mm, and preferably about 3.0 mm.

[0074] Thus, most preferably, the eyelet extends a distance of 1.5 mm to 3.5 mm from the elongated body, creating a perfect balance between easy detection under dilated pupils, no adverse effects on the patient's vision, and easy pick-up.

[0075] In certain embodiments, the eyelet includes a connector portion and a gripping portion, whereby the eyelet is attached to the elongate body via the connector portion, which serves as a base from which the eyelet further extends. Preferably, the connector portion is oriented as a continuation of the elongate body, and the gripping portion of the eyelet includes an opening that extends perpendicularly from the connector portion.

[0076] In a further preferred embodiment, the eyelet further comprises a joint between the gripping portion and the connecting portion, the joint comprising a narrowed portion having a width less than that of the gripping portion. In particular, the gripping portion forms an elongated extension having a length much greater than its width. All the measures taken in these embodiments allow high flexibility of the eyelet and straightening (and / or folding) with the elongated body for insertion and removal of the implant. The width of the joint is most preferably about 40% to about 75% of the width of the gripping portion, for example 0.2 mm to 1.0 mm for a gripping portion width of 0.5 mm to 1.4 mm. Preferably, the ratio is about 50% to about 60%, most preferably about 55% (for example, in the range of 0.3 mm to 0.55 mm for a range of 0.6 mm to 0.9 mm, or about 0.41 mm for about 0.74 mm).

[0077] In an alternatively preferred embodiment (FIG. 2A), the gripping portion includes an opening that extends partially into the junction of the eyelet, resulting in a portion of the junction that is reduced in cross-sectional dimension from the periphery of the junction (and typically has a smaller cross-sectional dimension than the body of the device), in order to optimize straightening. Preferably, the ratio of the reduced cross-sectional dimension of the junction compared to the cross-sectional dimension of the adjacent portions is about 45%-70%, preferably about 50%-65%, more preferably about 55%-60%. The opening extends into the junction, thereby defining a constriction, whereby said constriction has a minimum width at the dimension where the gripping portion extends from the elongate body, which minimum width of the constriction is less than the minimum width at the periphery of the junction. It is noted that in this particular embodiment, the body can be folded over on itself.

[0078] It should be noted that combinations of any two or more of the above embodiments, as well as the following, are considered to form part of the present invention, with such combinations providing particularly preferred embodiments of the invention.

[0079] In a preferred embodiment, the two (sealed) ends and the eyelet are made of a single polymer. In another preferred embodiment, the two (sealed) ends and the eyelet are made of a combination of two or more polymers. It should be noted that the polymers or polymer compositions used for one (sealed) end, the other (sealed) end, and the eyelet are completely independent of each other.

[0080] In some embodiments, the two (sealed) ends are contained within the eyelet, in the sense that they are directly connected to the eyelet. In some embodiments, one (sealed) end is contained within the eyelet and the other (sealed) end is not. In some embodiments, the one (sealed) end, the other (sealed) end, and the eyelet are separated from each other.

[0081] The manufacturing process of the eyelets can be accomplished by a number of techniques known to those skilled in the art. The maximum melting temperature of the polymer contained in the eyelets is preferably 200°C.

[0082] To aid in the withdrawal of the sustained release intraocular drug delivery device, the eyelet contains an opening that allows the introduction of classical instruments to pick up and remove the implant from the eye. This opening ensures withdrawal of the drug delivery device. To be visible to the physician and not affect the injectability, the diameter of the opening is in the range of 0.1-1 mm, preferably 0.2-0.8 mm, more preferably 0.25-0.6 mm, and even more preferably 0.3-0.45 mm.

[0083] To define such an opening, the material is arranged as two arms, the minimum cross-sectional dimension of which is 0.15 mm, preferably 0.2 mm for manufacturing considerations. Preferably, the maximum cross-sectional dimension / thickness of the arms is 0.8 mm, more preferably at most 0.6 mm, or at most 0.4 mm. In general, thinner arms are preferred, as long as strength is maintained to allow for handling of the eyelet. The disclosed width ranges ensure sufficient rigidity to maintain the opening and sufficient flexibility to allow for handling, while at the same time causing minimal disruption to the patient.

[0084] Considering the opening and the arms defining it, the lateral dimension of the gripping portion in the plane defined by the opening is in the range of 0.5-1.4 mm, preferably 0.6-0.9 mm, more preferably 0.7-0.8 mm. It should be noted that the connecting portion, which is a continuation of the device body itself, may have a larger lateral dimension in said plane.

[0085] To better aid in withdrawal of the drug delivery device, but avoid possible injury to the eye and damage to the eyelet itself, the eyelet must also follow certain rules regarding mechanical resistance. In current applications, the minimum resistance is close to 0.1 Newton, 0.5 N, or 1 N.

[0086] Injection / implantation of the drug delivery device is preferably accomplished by an injector, which requires the drug delivery device to be "straightened". To avoid affecting this feature, in a preferred embodiment, the junction where the connecting part and the gripping part are joined shall include a narrowed portion having a width (in the plane of the eyelet) smaller than the cross-sectional diameter of the elongate body and / or the gripping part of the eyelet. Furthermore, the thickness of the eyelet (the dimension perpendicular to the eyelet) should preferably be smaller than the cross-sectional diameter of the elongate body.

[0087] FIG. 1A shows a preferred embodiment of a sustained release intraocular drug delivery device with a first version of an eyelet, and FIG. 1B shows dimensional details.

[0088] The elongated body (3) is configured to form a non-closed ring, which is further processed to form a closed loop, preferably a torus. The eyelet (2) is configured to complete the ring and is connected to the body (3) of the sustained release intraocular drug delivery device (1) at two attachment points (4, 5), which also seal the two ends of the elongated body (3), respectively. The eyelet further includes a gripping portion (8) having an opening (6) and a connecting portion (7) connecting the gripping portion (containing the opening) to the attachment point, with the tip of the gripping portion (8) pointing toward the center of the ring. The eyelet includes a joint portion (10) connecting the gripping portion (8) to the connecting portion (7), with the connecting portion (7) configured to have the same cross-sectional dimensions as the elongated body (3). The joint portion (10) includes a narrowed portion (11) adjacent the connecting portion (7) to allow the eyelet to be folded against the ring body for straightening.

[0089] FIG. 2A shows a second preferred embodiment of a sustained release intraocular drug delivery device with a second version of the eyelet.

[0090] The elongated body (3) is configured to form a non-closed ring, which is further processed to form a closed loop, preferably a torus. The eyelet (2) is configured to complete the ring and is connected to the body (3) of the sustained release intraocular drug delivery device (1) at two attachment points (4, 5), which also seal the two ends of the elongated body (3), respectively. The eyelet further includes a gripping portion (8) including an opening (6) and a connecting portion (7) connecting the gripping portion to the attachment points, with the tip of the gripping portion (8) pointing toward the center of the ring. The eyelet includes a joint (10) connecting the gripping portion (8) and the connecting portion (7). It is noted that the connecting portion (7) is configured with generally the same cross-sectional dimensions as the elongated body (3), except for the constriction through which the opening extends. Importantly, it should be noted that at the location where the connecting portion (7) connects to the gripping portion (8), specifically between the two connection points, the junction (10) narrows. At this location, the opening (6) of the gripping portion (8) extends into the connecting portion (7). This is shown, for example, in the side views of Figures 2A and 2B. In particular, the reduction in the cross-sectional dimension of the connecting portion in the plane defined by the opening (6) is at least 25%, preferably at least 33% or 40%, since this improves the straightening. For example, in Figures 2A-2B, this is shown by the cross-sectional dimension of the ring itself being about 0.33 mm, while at the junction, the cross-sectional dimension where the opening (6) extends into the connecting portion is about 0.19 mm.

[0091] 3A and 3B show a third preferred embodiment of a sustained release intraocular drug delivery device with a third version of an eyelet.

[0092] The elongated body (3) is configured to form a non-closed ring, which is further processed to form a closed loop, preferably a torus. The eyelet (2) is configured to complete the ring and is connected to the body (3) of the sustained release intraocular drug delivery device (1) at two attachment points (4, 5), which also seal the two ends of the elongated body (3), respectively. The eyelet further includes a gripping portion (8) containing an opening (6), which may or may not be a round circle, and a connecting portion (7) connecting said gripping portion to the ring at the attachment point, with the tip of the gripping portion (8) pointing towards the center of the ring. The connecting portion (7) is connected to the gripping portion (8) via a joint (10). It should be noted that the connecting portion (7) is preferably configured with the same cross-sectional dimensions as the elongated body (3), and the joint (10) is narrowed all the way between the connecting portion (7) and the gripping portion (8), allowing the eyelet to be folded against the ring body (3) for straightening. More importantly, the transition from the joint to the connection may itself be rounded, as can be seen in the figures.

[0093] The preferred embodiments of the present invention are described below. However, it is clear that other embodiments are easily conceivable within the scope of the present invention. Therefore, the following presentation should not be interpreted as limiting, and those skilled in the art should understand that they will easily apply modifications to the presented examples without reevaluating the scope of the attached claims. EXAMPLES

[0094] Example 1 1A and 1B show a first preferred embodiment of a sustained release intraocular drug delivery device with a first version of an eyelet.

[0095] The elongated body (3) is configured to form a non-closed, approximately 360° ring shape (e.g., 350°). The eyelet (2) is connected to the body (3) of the sustained release intraocular drug delivery device (1) at two attachment points (4, 5) configured to fill the ring, which also seal the two ends of the elongated body (3), respectively. The eyelet further includes a gripping portion (8) and a connecting portion (7), with the tip of the gripping portion (8) pointing toward the center of the ring. The connecting portion (7) is essentially a continuation of the ring itself, connecting the two ends of the body (3) to each other. The connecting portion is connected to the gripping portion via a joint (10) that includes a narrowing portion (11).

[0096] The eyelet (which includes the two attachment points) does not include a therapeutic agent and is made of a polymer that is compatible with a polymer included in the drug delivery device, including a core polymer, a coating polymer, or another polymer.

[0097] FIG. 1B shows the dimensional details of the sustained release intraocular drug delivery device (1). The elongated cylinder has a cross-sectional diameter D of 0.33 mm, forming a ring with an outer diameter of about 11 mm. The eyelet (2) has a total length L of about 2.50 mm, width W of 0.74 mm (see FIG. 1A), and thickness T of 0.22 mm, which is thinner than the cross-section of the connector (7), further favoring straightening into the injector device (FIG. 1B). The eyelet is planar symmetrical about a plane perpendicular to the body through the longitudinal axis of the eyelet and about a plane parallel to the body through the longitudinal axis of the eyelet, and is perfectly rounded in cross-section.

[0098] The length of the opening (6) is about 0.77 mm (O) and the width (lateral) is about 0.30 mm. The bottom of the opening (6) is about 0.33 mm (B) from the tip (8). The two arms (12) of the opening (6) along the length are configured like a cylinder with a cross section of about 0.22 mm. However, it should be understood that variations in shape may exist, such as oval, square, etc. The joint (10) gradually narrows from the top of the gripping portion (6) towards the connecting portion (7), and the narrowest part may reach 0.41 mm at the constriction (11). The joint (10) is rounded at the point where it meets the connecting portion (7) into a circle, preferably with a radius of 0.20 mm. However, it should be noted that the radius of said circle may vary from 0.10 mm to 0.30 mm, preferably from 0.15 mm to 0.25 mm.

[0099] In the most preferred embodiment, the joint portion (10) branches off from the narrowed portion (11) toward the gripping portion (8) at an angle of 20° to 30°, preferably about 25°, as seen in FIG. 1A.

[0100] Example 2 2A and 2B show a second preferred embodiment of a sustained release intraocular drug delivery device with a second version of the eyelet.

[0101] The elongated body (3) is configured to form a non-closed, approximately 360° ring shape (e.g., 350°). The eyelet (2) is connected to the body (3) of the sustained release intraocular drug delivery device (1) at two attachment points (4, 5) configured to fill the ring, which also seal the two ends of the elongated body (3), respectively. The eyelet further includes a gripping portion (8) including an opening (6) and a connecting portion (7), the tip of the gripping portion facing the center of the ring. A joint (10) connects the gripping portion and the connecting portion, narrowing where the connecting portion connects to the gripping portion, and the connecting portion (7) is configured with the same cross-sectional dimensions as the elongated body (3). The opening (6) extends into the connecting portion at the joint, as seen in Figures 2A-2B. The cross-sectional dimension RD where the opening (6) extends into the connection is approximately 0.19 mm, in comparison with the diameter D of the body surrounding said reduced portion, which is approximately 0.33 mm.

[0102] The eyelet (which includes the two attachment points) does not include a therapeutic agent and is made of a polymer that is compatible with polymers included in the drug delivery device, including core polymers, coating polymers or other polymers.

[0103] FIG. 2B shows the dimensional details of a detailed embodiment of the sustained release intraocular drug delivery device (1). The elongated cylindrical (it should be understood that there may be variations in shape, such as oval, square, etc.) body has a cross-sectional diameter D of about 0.33 mm. The eyelet (2) has a total length L of about 2.50 mm, a lateral dimension W (perpendicular to the direction extending from the body and lying in the plane defined by the opening) of about 0.74 mm, and a thickness T of about 0.22 mm. This means that it is thinner than the cross-section of the link (7) (FIG. 2B), further favoring alignment into the injector device. The eyelet is planar symmetrical with respect to a plane perpendicular to the body through the longitudinal axis of the eyelet, and planar symmetrical with respect to a plane parallel to the body through the longitudinal axis of the eyelet, and is substantially perfectly rounded in cross-section.

[0104] Opening O (6) has a longitudinal dimension of 2.09 mm and a transverse dimension of 0.30 mm. The cross-sectional diameter B of the two arms along the length of opening (6) is approximately 0.22 mm. Joint (10) is rounded into a circle with a radius of 0.10 mm at the point where it meets connecting portion (7), but this can vary between R0.05 and R0.30 mm, preferably R0.075 and R0.15 mm.

[0105] Example 3 3A and 3B show a third preferred embodiment of a sustained release intraocular drug delivery device with a third version of an eyelet.

[0106] The elongated body (3) is configured to form a non-closed, approximately 360° ring shape (e.g., 350°). The eyelet (2) is connected to the body (3) of the sustained release intraocular drug delivery device (1) at two attachment points (4, 5) configured to fill the ring, which also seal the two ends of the elongated body (3), respectively. The eyelet further includes a gripping portion (8) and a connecting portion (7), with the tip of the gripping portion (8) pointing toward the center of the ring. The connecting portion is connected to the gripping portion via a joint (10) that is narrower than the gripping portion so that the eyelet can be folded against the ring body for straightening.

[0107] The eyelet (which includes the two attachment points) does not include a therapeutic agent and is made of a polymer that is compatible with a polymer included in the drug delivery device, including a core polymer, a coating polymer, or another polymer.

[0108] The eyelet is substantially completely rounded in cross section, with plane symmetry with respect to a plane perpendicular to the body passing through the longitudinal axis of the eyelet and with plane symmetry with respect to a plane parallel to the body passing through the longitudinal axis of the eyelet. The gripping portion (8) around the opening (6) is configured in a ring shape. The joint portion (10) is configured as a cylindrical (it should be understood that there may be variations in shape, such as oval, square, etc.) portion connecting the gripping portion and the connecting portion. The joint portion (10) is thinner than the opening and the gripping portion to favor straightening into the injector device. Preferably, the joint portion (10) is rounded at the point where it meets the connecting portion (7), more preferably rounded into a circle with a radius varying from R0.05 to R0.30 mm, preferably R0.075 to R0.15 mm.

[0109] Figure 3B shows dimensional details of the eyelet of device (1) of Figure 3A. In this embodiment, the length L of the eyelet is similar to Examples 1 and 2, about 2.5 cm, and the opening O is about 0.3-0.4 cm in diameter, although these dimensions are not meant to be limiting and serve only as further examples. The gripping portion (8) around the opening (6) has a cross-sectional diameter T of about 0.22 mm, and the joint portion (10) has a width D (diameter) of about 0.33 cm. The elongated body is circular with a diameter of about 10-11 cm, and the body itself is cylindrical with a diameter of about 0.33 cm.

[0110] Example 4 Example 4 illustrates the preparation of a sustained release intraocular drug delivery device according to the preferred embodiments of Examples 1-3 and / or thereafter. The steps are: providing an elongate body comprising a polymer matrix core and a polymer coating completely surrounding said polymer matrix, at least one therapeutic agent being admixed with the polymer matrix core, the polymer coating controlling a release rate of the therapeutic agent, and two ends of the elongate body being unsealed; positioning the elongated body in a die for forming it into a 350° ring, the elongated body having a predetermined length to accurately form such a non-closed ring; adding a polymer to the mold to form the eyelet of Example 1, 2 or 3 and / or any other embodiment of an eyelet according to the present disclosure, wherein the polymer also seals and joins the two ends of the elongate body to complete the device into a complete ring;

[0111] Example 5 Example 5 illustrates the preparation of a sustained release intraocular drug delivery device according to the preferred embodiments of Examples 4 and / or thereafter. The steps are: providing an elongate body comprising a polymer matrix core and a polymer coating completely surrounding the polymer matrix, at least one therapeutic agent being admixed with the polymer matrix core, the polymer coating controlling a release rate of the therapeutic agent, one end of the elongate body being sealed and the other end being unsealed; positioning the elongate body in a mold that may or may not form the elongate body into a particular shape; and pouring a polymer into the mold to form an eyelet according to Example 4 and / or any other embodiment of an eyelet according to the present specification, wherein the polymer also seals one end of the elongate body that was not sealed in the previous step.

Claims

1. A sustained release intraocular drug delivery device (1) comprising an elongated body (3) including two ends and eyelets (2) fixedly connected to both ends of the elongated body; The elongate body (3) further comprises a substantially elongate polymer matrix core in which at least one therapeutic agent is mixed, and a covering completely surrounding the matrix core, the covering comprising, preferably being, a polymer coating; A sustained release intraocular drug delivery device, wherein the eyelet (2) is adapted to aid in withdrawal of the device (1), and the eyelet (2) is essentially free of a therapeutic agent.

2. The sustained-release intraocular drug delivery device (1) of claim 1, wherein the eyelet includes a gripping portion (8) and a connecting portion (7), and the connecting portion (7) connects the gripping portion (8) to at least one end, preferably both ends, of the main body.

3. The sustained release intraocular drug delivery device (1) according to claim 1 or 2, wherein the gripping portion (8) includes an opening (6).

4. A sustained-release intraocular drug delivery device (1) as described in claim 1 or 2, further comprising a narrowed portion (11) included in the connecting portion (7) or located between the gripping portion (8) and the connecting portion (7), the narrowed portion (11) facilitating folding of the drug delivery device (1).

5. A sustained release intraocular drug delivery device (1) as described in claim 1 or 2, wherein the ends (4, 5) of the elongated body (3) are sealed, the sealed ends (4, 5) do not contain a therapeutic agent, and at least one sealed end (4, 5) is sealed by the eyelet (2), and preferably both ends (4, 5) are sealed by the eyelet (2).

6. The sustained release intraocular drug delivery device (1) of claim 1 or 2, wherein the eyelet (2) comprises one or more of the following polymers: ethylene-vinyl acetate (EVA), poly(dimethylsiloxane) or PDMS, polyolefin, polyethylene, polyurethane, poly(methyl methacrylate) or PMMA, and cross-linked polyvinyl alcohol, or a combination thereof.

7. 7. The sustained release intraocular drug delivery device (1) of claim 6, wherein the polymer constituting the eyelet (2) is compatible with the polymer contained in the elongate body (3), and the polymer of the elongate body (3) comprises: ethylene-vinyl acetate (EVA), poly(dimethylsiloxane) or PDMS, polyolefin, polyethylene, polyurethane, poly(methyl methacrylate) or PMMA, thermoplastic polyurethane (TPU), and cross-linked polyvinyl alcohol, or a combination thereof.

8. A sustained-release intraocular drug delivery device (1) as described in claim 1 or 2, wherein the eyelet (2) further includes a joint (10) connecting the gripping portion (8) and the connecting portion (7), and the joint (10) includes the narrowed portion (11).

9. The sustained-release intraocular drug delivery device (1) of claim 1 or 2, wherein the gripping portion (8) and the connecting portion (7) are directly connected, and the opening (6) of the gripping portion (8) extends partially into the connecting portion (7), thereby defining the narrowed portion (11), whereby the narrowed portion (11) has a minimum width in the dimension where the gripping portion (8) extends from the elongated body (3), and the minimum width of the narrowed portion (11) is smaller than the minimum width in the dimension of the surrounding portion of the connecting portion (7).

10. A sustained-release intraocular drug delivery device (1) as described in claim 1 or 2, wherein the device (1) is a 360° ring and the eyelet (2) is attached to the device (1) at two attachment points (4, 5), which respectively seal two ends of the elongated body (3) of the device (1), and preferably the eyelet (2) protrudes toward the center of the ring.

11. 3. The sustained release intraocular drug delivery device (1) according to claim 1 or 2, wherein the device (1) is in a folded configuration suitable for injection into the eye using an injection device.

12. 3. The sustained release intraocular drug delivery device (1) of claim 1 or 2, wherein the eyelet (2) extends from the elongate body (3) over a distance in the range of 1.0 mm to 3.5 mm, preferably 1.5 mm to 3.0 mm, more preferably 1.7 mm to 2.7 mm, and even more preferably 2.0 mm to 2.6 mm.

13. 3. The sustained release intraocular drug delivery device (1) of claim 1 or 2, wherein the maximum width dimension of the eyelet opening (6) is in the range of 0.1 mm to 1.0 mm, preferably 0.2 mm to 0.6 mm, more preferably 0.25 mm to 0.4 mm.

14. 3. The sustained release intraocular drug delivery device (1) of claim 1 or 2, wherein the opening (6) is defined by two arms joined at their respective ends, the minimum width of the arms being 0.15 mm.

15. 3. The sustained-release intraocular drug delivery device (1) according to claim 1 or 2, wherein the lateral dimension of the gripping portion (8) in the plane defined by the opening (6) is in the range of 0.5 mm to 1.4 mm, preferably 0.6 mm to 0.9 mm, and most preferably about 0.7 mm to 0.8 mm.

16. A process for preparing a removable sustained release intraocular drug delivery device, preferably as claimed in claim 1 or 2, comprising: - providing an elongate body (3) comprising a polymer matrix core and a polymer coating completely surrounding said polymer matrix, wherein at least one therapeutic agent is mixed into said polymer matrix core, and wherein two ends of said elongate body are not sealed; - positioning said elongate body in a mould that forms it into a substantially 360° ring; - adding at least one polymer to form eyelets (2), said polymer also sealing the two ends (4, 5) of said elongate body (3).

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