US20050059956A1 - Devices for intraocular drug delivery - Google Patents
Devices for intraocular drug delivery Download PDFInfo
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- US20050059956A1 US20050059956A1 US10/823,089 US82308904A US2005059956A1 US 20050059956 A1 US20050059956 A1 US 20050059956A1 US 82308904 A US82308904 A US 82308904A US 2005059956 A1 US2005059956 A1 US 2005059956A1
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- Prior art keywords
- body member
- eye
- delivery
- shape
- substance
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
- A61K9/0051—Ocular inserts, ocular implants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F9/00—Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
- A61F9/0008—Introducing ophthalmic products into the ocular cavity or retaining products therein
- A61F9/0017—Introducing ophthalmic products into the ocular cavity or retaining products therein implantable in, or in contact with, the eye, e.g. ocular inserts
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B2017/00831—Material properties
- A61B2017/00867—Material properties shape memory effect
Definitions
- the present invention relates to a device and method for intraocular delivery of therapeutic agents.
- Preferred devices of the invention include a non-linear portion that resides within a patient's eye during use that can facilitate the delivery of a therapeutic agent.
- the delivery of drugs to the eye presents many challenges.
- the ocular absorption of systemically administered pharmacologic agents is limited by the blood ocular barrier, namely the tight junctions of the retinal pigment epithelium and vascular endothelial cells. High systemic doses can penetrate this blood ocular barrier in relatively small amounts, but expose the patient to the risk of systemic toxicity.
- Topical delivery of drugs often results in limited ocular absorption due to the complex hydrophobic/hydrophilic properties of the cornea and sclera. Additionally, topical agents are mechanically removed by the blink mechanism such that only approximately 15% of a single drop is absorbed. Diffusion of topically administered drugs to the posterior chamber occurs, but often at sub-therapeutic levels.
- Intravitreal injection of drugs is an effective means of delivering a drug to the posterior segment in high concentrations.
- these repeated intraocular injections carry the risk of infection, hemorrhage and retinal detachment. Patients also find this procedure somewhat difficult to endure.
- U.S. Pat. No. 4,300,557 describes an intraocular implant in the form of a silicone capsule, which can be filled with a drug to be delivered.
- the implant is inserted through an incision into the vitreous region of the eye. After insertion of the implant, the incision is closed and the capsule remains in place for a period of time.
- Attached to the implant is a tube that passes through the surface of the eye. The tube may be used for subsequent injection of a drug while the implant is in the eye.
- the implant may be removed by making a second surgical incision into the eye and retrieving the implant. While in the vitreous, the device is not anchored and may move about freely.
- the overall shape of the capsule is linear, the amount of drug that may held by the device and that may be delivered over the surface area of the device is limited. If the width of the capsule is increased, excessive sized incisions will be required for insertion of the device. If the length of the capsule is increased to greater than 1 cm, the implant will pass into the central visual field of the eye, thereby causing blind spots in the patient's eye as well as increase risk of damage to the retinal tissue and lens capsule.
- U.S. Pat. No. 5,378,475 describes a device which has been developed for insertion in the vitreous region of the eye, and is described in T. J. Smith et al., Sustained-Release Ganciclovir, Arch. Ophthalmol, 110, 255-258 (1992) and G. E. Sanborn, et al., Sustained-Release Ganciclovir Therapy for Treatment of Cytomegalovirus Retinitis. Use of an Intravitreal Device, Arch. Ophthalmol, 110, 188-195 (1992).
- This device consists of an inner core of pharmacologic agent surrounded by two coatings with different permeabilities. Drug diffuses through a small opening in one of these coatings achieving near-order release kinetics.
- the device is membrane diffusion drug delivery system that relies on EVA/PVA polymers to mediate release rate.
- EVA/PVA polymers to mediate release rate.
- agents cannot be effectively delivered from such a system because their permeation rate through the rate controlling material of the system is too small to produce a useful effect.
- Other agents cannot be satisfactorily delivered by diffusional devices because of a particular chemical characteristic of the agent. This includes salts, because of their ionic character, and unstable polar compounds that cannot be formulated into a composition suitable for storage and delivery from such systems.
- U.S. Pat. No. 5,098,443 describes certain specific implants that are inserted through incisions made in the eye wall or sutured around the globe of the eye. These rings may be formed from biodegradable polymers containing microparticles of drug. Alternatively, the implant may be in the form of a hollow flexible polymeric cocoon with the drug disposed therewithin for slow release by osmosis. No anchoring device is described.
- U.S. Pat. No. 5,466,233 describes a certain tack for intraocular drug delivery.
- This device has an end that is positioned in the vitreous cavity while the head remains external to the eye and abuts the scleral surface.
- the tack contains a fixation portion to attempt to retain attachment within the eye. Because the overall shape of the capsule is linear, the amount of drug that may held by the device and the surface area through which the drug may be delivered is limited. If the width of the capsule is increased, excessive sized incisions will be required for insertion of the device. If the length of the capsule is increased to greater than 1 cm, the implant will pass into the central visual field of the eye, thereby causing blind spots in the patient's eyes well as increase risk of damage to the retinal tissue and lens capsule.
- the present invention provides methods and devices for the intraocular delivery of substances including, for example, therapeutic agents and medicaments.
- Preferred devices of the invention have a non-linear shape during residence within a patient's eye.
- Preferred designs have multiple turns or angles, particularly substantially coil or helical configurations, at least for those portions that reside within a patient's eye during use.
- Preferred device of the invention also include those that have a quite small cross-section shape, at least with respect to areas that reside within a patient's eye during use. Such devices can be implanted by minimally invasive surgical procedures, including without the need for any sutures to implant or after use of the use.
- An exemplary embodiment of the delivery device includes a body member that is non-linear in shape.
- the device has a non-linear shape before, during and after the device is inserted into the eye.
- the device is fabricated of a “shape memory” material wherein the device is linear as it is inserted into the eye and wherein the device takes on a non-linear shape once it is implanted in the eye.
- shape memory materials include known materials such as, for example, shape memory alloys (SMA) like nitinol, shape memory polymers (SMP) like AB-polymer networks based on oligo(e-caprolactone) dimethacrylates and n-butyl acrylate.
- the non-linear shape of the body member provides a number of advantages.
- the non-linear shape provides a built-in anchoring mechanism that prevents unwanted movement of the device and unwanted ejection of the device out of the eye since the non-linear shape of the body member requires manipulation of the device to get it out of an incision.
- the device can be removed only by twisting the device out of the eye and, thus, is not susceptible to ejection by the eye or unwanted movement within the eye.
- the non-linear shape geometry of the body member provides greater surface area per length of the device. This is advantageous because it is desirable to limit the length of drug delivery implants to prevent the implant from entering the central visual field (See FIG.
- the implant enters the central visual field, this will result in blind spots in the patient's vision and will increase the risk of damage to the retina tissue and lens capsule.
- the device of the present invention holds a greater volume of materials per length of the device and it also provides a larger surface area per length of the device through which the material may be delivered.
- the delivery device may further include a rim or cap at its proximal end.
- the device is inserted into the eye through an incision until the rim or cap abuts the incision. If desired, the rim or cap may then be sutured to the eye to further stabilize and prevent the device from moving once it is implanted in its desired location.
- body member has a lumen extending along its length for housing the substance to be delivered.
- a port in fluid communication with the lumen is located at the proximal end of the device. This allows for filling and refilling of the device after the device has been implanted in the eye.
- the substance in the lumen can then be delivered to the eye by a delivery mechanism.
- the lumen in some embodiments, may further include a number of dividers to form a plurality of compartments each of which could be filled with a different substance, thereby allowing for delivery of more that one substances by the same device at the same time, if desired.
- the delivery mechanism comprises one or more exit apertures located at the distal end of the body member. In another embodiment, the delivery mechanism comprises a plurality of openings along the body member. In another embodiment, the delivery mechanism comprises the material forming the body member.
- the material forming the body member may be a material that is permeable or semi-permeable to the substance to be delivered.
- the body member is fabricated of a synthetic biodegradable polymer containing microparticles of the substance to be delivered. As the polymer decomposes, the substance to be delivered is released into the eye.
- FIG. 1 illustrates transcleral placement of the delivery device in accordance with one embodiment of the present invention.
- FIG. 2 a illustrates the delivery device in accordance with one embodiment of the present invention.
- FIG. 2 b is an enlarged view of a portion of the body member of the delivery device shown in FIG. 2 a showing the lumen.
- FIG. 2 c is an enlarged cross-sectional view of the body member of the delivery device shown in FIG. 2 a.
- FIG. 3 a illustrates the delivery device having a delivery mechanism in accordance with one embodiment of the present invention.
- FIG. 3 b illustrates the delivery device having a delivery mechanism in accordance with another embodiment of the present invention.
- FIG. 3 c illustrates the delivery device having a delivery mechanism in accordance with another embodiment of the present invention.
- FIG. 4 a is an enlarged view of a portion of the body member of the delivery device in accordance with another embodiment of the present invention showing a plurality of lumen.
- FIG. 4 b is an exploded view of the cap or rim and a portion of the body member shown in FIG. 4 a showing one arrangement of a plurality of lumen.
- FIG. 4 c is an exploded view of the cap or rim and a portion of the body member shown in FIG. 4 a showing another arrangement of a plurality of lumen.
- FIG. 4 d illustrates another embodiment of the body member comprising a cluster of tubes.
- FIG. 5 a illustrates the delivery device in accordance with another embodiment of the present invention showing a lumen separated into a plurality of compartments.
- FIG. 5 b shows the delivery device of FIG. 5 a and further shows one type of delivery mechanism in accordance with the present invention.
- FIG. 6 shows a shows a cross-sectional view of an eye illustrating the central visual field of the eye.
- FIG. 7 shows a cross-sectional schematic view of an eye illustrating one technique of pulling back of the conjunctiva to provide access into the eye for insertion of the delivery device of the present invention.
- preferred delivery devices of the invention have a non-linear (arcuate) shape during residence within a patient's eye.
- Preferred designs have multiple turns or angles.
- preferred designs the device has at least two, three, four, five, six, seven, right, nine or ten separate deviations from a linear path.
- a coil design is particularly preferred, although other multiple-angle configurations are also suitable such as a substantially Z-shape and the like.
- the delivery device 1 includes a non-linear shaped body member 2 having a proximal end 4 , a distal end 6 .
- the body member 2 has a coil shape, as shown in FIGS. 1-5 c .
- the shape of the body member 2 is not limited to a coil shape and other non-linear shapes may be used such as, for example, other random curled shapes, a zig-zag shape, a “J” shape and the like.
- a substantially “C” shape configuration is less preferred.
- the non-linear shape of the body member 2 provides a number of advantages.
- the large intravitreal surface area provided by the non-linear shape geometry of the body member 2 can allow for more optimal sustained release of the substance through diffusion, enzymatic degradation, active pumping and other types of delivery.
- it is desirable to limit the length “L” of drug delivery implants prevent the drug delivery implant from entering the central visual field “A” (See FIG. 6 ). If the implant enters the central visual field A, this will result in blind spots in the patient's vision and will increase the risk of damage to the retina tissue and lens capsule.
- the distance from the implantation site on the pars plana to the central visual field is approximately 1 cm.
- the overall length of the implant is preferably less than 1 cm.
- the non-linear shape of the body member 2 provides a built-in anchoring system that prevents unwanted movement of the device and unwanted ejection of the device out of the eye since the non-linear shape of the body member requires manipulation of the device to get it out of an incision (e.g. a coil-shaped body member 2 would require twisting the device out of the eye, and a zig-zag shaped body member 2 would require moving the device back and forth to remove the device from the eye).
- the delivery device has a coil-shaped body member 2 as shown in FIGS. 1-5 c .
- the coil shape of the device provides a large intravitreal surface area through which material can be delivered.
- the coil shape of the body member allows the device to be screwed or twisted into the eye through an incision approximately the same size as the outer diameter of the tube forming the body member 2 .
- the coil shape of the body member acts as an anchoring mechanism that holds the delivery device 1 within the eye and prevents unwanted movement of the delivery device and unwanted ejection of the delivery device 1 out of the eye. Due to the coil shape, the delivery device 1 must be twisted and unscrewed out of the eye.
- the materials used in fabricating the body member 2 are not particularly limited, provided these materials are biocompatible. Preferably, these materials are also insoluble in the body fluids and tissues that the device comes into contact with. It is further preferred that the body member 2 is fabricated of a flexible material so that small movements of the delivery device will not be translated to the retina, thereby minimizing the risk of retinal tearing, detachment and other damage. In some embodiments, as described in further detail below, it is preferable that at least the distal end 6 of body member 2 is fabricated of a rigid, non-pliable material.
- the material used to form the body member 2 is permeable or semi-permeable to the substance to be delivered.
- the body member is fabricated of a material having shape memory and/or superelastic characteristics.
- the body member 2 is fabricated of a nonbiodegradable polymer.
- nonbiodegradable polymers are well-known and may include, for example, polymethylmethacrylate, a silicone elastomer, or silicone rubber.
- Other suitable non-erodible, biocompatible polymers which may be used in fabricating the body member 2 may include polyolefins such as polypropylene and polyethylene, homopolymers, and copolymers of vinyl acetate such as ethylene vinyl acetate copolymer, polyvinylchlorides, homopolymers and copolymers of acrylates such as polyethylmethacrylate, polyurethanes, polyvinylpyrrolidone, 2-pyrrolidone, polyacrylonitrile butadiene, polycarbonates, polyamides, fluoropolymers such as polytetrafluoroethylene and polyvinyl fluoride, polystyrenes, homopolymers and copolymers of styrene acrylon
- the body member 2 of the delivery device 1 can, in one embodiment, have a non-linear shape prior to, during and after insertion of the device into the eye.
- the delivery device 1 can be fabricated of a material having shape memory and/or superelastic characteristics that allows the device to be deformed and made, for example, linear, for easier insertion into the eye and which returns to its original shape after it is inserted into the eye.
- the delivery device 1 has a “memory shape” that it will take on under certain conditions.
- the delivery device 1 may have a zig-zag or coiled memory shape.
- the surgeon may deform the delivery device 1 into a linear shape for quick and easy insertion of the device through an incision the size of the cross section of the linear shaped device.
- the device can then take on its zig-zag, coiled or other memory shape.
- Shape memory alloys SMA
- Ni—Ti alloy nitinol
- SMP shape memory polymers
- Shape memory alloys generally have at least two phases: (1) a martensite phase, which has a relatively low tensile strength and which is stable at relatively low temperatures, and (2) an austenite phase, which has a relatively high tensile strength and which is stable at temperatures higher than the martensite phase.
- the shape memory characteristics are imparted on the material by heating the material to a temperature above the temperature at which the austenite phase is stable. While the material is heated to this temperature, the device is held in the “memory shape”, which is shape that is desired to be “remembered”.
- Such materials and methods of imparting shape memory characteristics are further described in, for example, U.S. Pat. No. 4,665,905, U.S. Pat. No. 4,925,445 and U.S. Pat. No. 6,245,100.
- the delivery device of the present invention takes advantage of the superelastic properties of the material to extend the device into a linear shape. Once injected into the eye in an unconstrained form, the device will retain its memory shape.
- the distal end 6 of the body member 2 may be blunt or, in some embodiments, it is pointed or has a beveled ramp-like configuration so that the distal end 6 may be used to pierce the eye during insertion. In one embodiment, the distal end 6 has a ramp-like angle of about 30°. If the distal end 6 of the body member 2 is used to pierce the eye during insertion, at least the distal end 6 is fabricated of a rigid, non-pliable material suitable for piercing the eye. Such materials are well known and may include, for example, polyimide and similar materials.
- a rim or cap 8 may further be located at the proximal end 4 of the body member 2 to assist in stabilizing the device 1 once implanted in the eye.
- the delivery device 1 is inserted into the eye through an incision until the rim or cap 8 abuts the incision. If desired, the rim or cap 8 may then be sutured to the eye to further stabilize and prevent the device from moving once it is implanted in its desired location.
- the overall size and shape of the rim or cap 8 is not particularly limited provided that irritation to the eye is limited.
- the rim or cap 8 is shown circular in shape, the rim or cap may be of any shape, for example, circular, rectangular, triangular, etc.
- the rim or cap 8 preferably has rounded edges.
- the rim or cap 8 is designed such that it remains outside the eye and, as such, the rim or cap 8 is sized so that it will not pass into the eye through the opening in the eye through which the device is inserted.
- the rim or cap 8 may further be designed such that it can be easily sutured or otherwise secured to the surface surrounding the opening in the eye and may, for example, contain a plurality of holes (not shown) through which sutures may pass.
- the materials used in fabricating the rim or cap 8 are not particularly limited, provided these materials are biocompatible and preferably insoluble in the body fluids and tissues that the device comes into contact with. Further, it is preferred that the rim or cap 8 is fabricated of a material that does not cause irritation to the portion of the eye that it contacts. As such, preferred materials are pliable and may include, by way of example, various polymers including, for example, silicone elastomers and rubbers, polyolefins, polyurethanes, acrylates, polycarbonates, polyamides, polyimides, polyesters, and polysulfones.
- the non-linear body member 2 is fabricated of a tube that is wound into a coiled shape.
- the tube forming the non-linear body member 2 is preferably cylindrical in shape, with a circular cross-section.
- the shape of the tube is not limited and, for example, may alternatively have square, rectangular, octagonal or other cross-sectional shapes.
- the tube has a lumen 10 extending along its length for housing the substance to be delivered. In one embodiment, the lumen 10 is filled with the substance prior to inserting the device into the eye.
- the lumen 10 may be filled with the substance after the delivery device has been inserted into the eye. This may be accomplished by providing a port 12 near the proximal end 4 of the body member 2 in fluid communication with the lumen 10 . This further allows for refilling of the device during use, if required.
- the port 12 is preferably designed such that the needle of a syringe, or similar injection mechanism, may be inserted into the port 12 and the substance injected by the syringe or injection mechanism. Thus, the substance travels through the port 12 and into the lumen 10 .
- the port 12 preferably forms a snug seal about the needle of the syringe or injection mechanism to prevent leakage of the substance out of the port 12 around the syringe needle or injection mechanism and to provide sterile injection of agent into the lumen 10 .
- fittings or collars (not shown), through which a syringe needle or injection mechanism may be inserted and which form a snug seal about the syringe needle or injection mechanism, may be mounted on the port 12 .
- the needle of the syringe or the injection mechanism is removed from the port 12 and the port 12 sealed. This may be accomplished by providing a removable cover (not shown) on the port 12 that may be removed for injection of the substance and replaced when the substance has been injected.
- the port 12 is fabricated of an injectable self-sealing material through which the needle or injection mechanism may be inserted and which seals off automatically when the needle or injection mechanism is removed.
- Such materials are known and include, for example, silicone rubber, silicone elastomers and polyolefin.
- the substance can then be delivered to the eye by a delivery mechanism.
- the delivery mechanism comprises an exit aperture 16 located at the distal end 6 of the body member 2 .
- a plurality of exit apertures 16 a located at the distal end 6 of the body member 2 may form the delivery mechanism.
- the number and size of the one or more exit apertures 16 may vary depending on the desired rate of delivery of the agent and may be readily determined by one of skill in the art.
- the one or more exit apertures 16 are designed such that the substance is slowly diffused rather than expelled as a fluid stream, which may damage the delicate tissues of the eye.
- this may be achieved by, for example, placing a covering or lining (not shown) over the distal exit aperture 16 , wherein the covering or lining has a particular porosity to the agent or wherein the covering or lining is fabricated of a diffusion or rate-limiting membrane, matrix material or similar material.
- the delivery mechanism comprises a plurality of openings 18 along the body member 2 .
- the number and size of the one or more openings 18 may vary depending on the desired rate of delivery of the agent and may be readily determined by one of skill in the art.
- the location of the plurality of openings 18 may be situated so as to deliver the substance at a particular location once the device is implanted in the eye.
- the plurality of openings 18 are designed such that the substance is slowly diffused rather than expelled as a fluid stream, which may damage the delicate tissues of the eye.
- an exit aperture 16 at the distal end 6 of the body member 2 as described above may also be included.
- the delivery mechanism comprises the material forming the body member 2 .
- the material forming the body member 2 may be a material that is permeable or semi-permeable to the substance to be delivered. Such materials may vary depending on the particular application and the substance to be delivered and may be readily determined by one of skill in the art.
- some suitable permeable materials may include polycarbonates, polyolefins, polyurethanes, copolymers of acrylonitrile, copolymers of polyvinyl chloride, polyamides, polysulphones, polystyrenes, polyvinyl fluorides, polyvinyl alcohols, polyvinyl esters, polyvinyl butyrate, polyvinyl acetate, polyvinylidene chlorides, polyvinylidene fluorides, polyimides, polyisoprene, polyisobutylene, polybutadiene, polyethylene, polyethers, polytetrafluoroethylene, polychloroethers, polymethylmethacrylate, polybutylmethacrylate, polyvinyl acetate, nylons, cellulose, gelatin, silicone rubbers and porous rubbers.
- the particular material used to fabricate the body member 2 may be chosen to provide a particular rate of delivery of the substance, which may be readily determined by one of skill in the art. Further, the rate of delivery of the substance may also be increased or decreased by varying the percentage of the body member 2 formed of the material permeable to the agent. Thus, for example, to provide a slower rate of delivery, the body member 2 may be fabricated of 50% or less permeable material. For example, the body member 2 may be fabricated of 1%, 5%, 10%, 20%, 30%, 40% or 50% of permeable material. For a faster rate of delivery, the body member 2 may be fabricated of greater than 50% of permeable material.
- the body member 2 may be fabricated of 51%, 55%, 60%, 70%, 80%, 90% or 100% of permeable material.
- the location of the permeable or semi-permeable material may be situated so as to deliver the substance at a particular location once the device is implanted in the eye.
- the body member 2 is fabricated of a synthetic biodegradable polymer containing microparticles of the substance to be delivered.
- the substance to be delivered is released into the eye. Release time is a function of the polymer and the shape and size of the body member 2 and may be readily determined by one of ordinary skill in the art.
- biodegradable polymers may vary depending on the particular application and may be readily determined by one of skill in the art.
- biodegradable polymers may include polyesters of molecular weight from about 4,000 to about 100,000, homopolymers and copolymers of polylactic acid and polyglycolic acid, polycaprolactone, homopolymers and copolymers of polyanhydrides such as terephthalic acid anhydride, bis(p-anhydride) and poly(p-carboxyphenoxy) alkyl, homopolymers and copolymers of dicarboxylic acids such as sebacic, adipic, oxalic, phthalic and maleic acid, polymeric fatty acid dimer compounds such as polydodecanedioic acid polyorthoesters, poly(alkyl-2-cyanoacrylate) such as poly(hexyl-2-cyanoacrylate), collagen (gelatin), polyacetals, divinyloxyalkylenes, polydihydropyrans, polyphosphazenes, homopolymers and copolymers of amino acids such as copolymers
- the non-linear body member 2 includes a plurality of lumens 10 a capable of housing and delivering a plurality of substances.
- each lumen 10 a may be in fluid communication with plurality of ports 12 a .
- These ports 12 a are similar to the single port 12 described above. (e.g. the ports 12 a may include a cover that may be removed for injection of the substance and replaced when the substance has been injected, or the ports 12 a may be fabricated of an injectable self-sealing material)
- the lumens 10 a and ports 12 a may be arranged such that each lumen 10 a may be filled with a different substance through the corresponding ports 12 a .
- the single device may be used to deliver more than one substance if desired.
- the plurality of lumens 10 a are situated in a ring about the outer circumference of the body member 2 as shown in FIG. 4 b .
- the substance(s) may be injected into the lumens 10 a for delivery through a delivery mechanism, which may be any of the delivery mechanisms described above or a combination of the delivery mechanisms described above.
- a plurality of lumen 10 a are clustered within the body member 2 as shown in FIG. 4 c .
- the substance(s) may be injected into the lumens 10 a for delivery through a delivery mechanism.
- the inner lumens 10 a preferably deliver their housed substances through one or more apertures 16 , 16 a located near the distal end 6 of the body member 2
- the outer lumens 10 a located at the outer circumference of the body member 2 may deliver their housed substances through one or more apertures 16 , 16 a located near the distal end 6 of the body member 2 , a plurality of openings 18 along the body member 2 , and/or through the material forming the body member 2 as described above.
- the non-linear body member 2 is formed of a plurality of tubes 20 clustered and wound into a coil shape as shown in FIG. 4 d .
- the substance(s) to be delivered is/are inserted into and housed within the plurality of hollow tubes 20 .
- the plurality of tubes 20 may contain different substances or the same substance as desired.
- the substances are then delivered by one or more of the delivery mechanisms set out above.
- one or more of the tubes 20 may have one or more exit apertures 22 at their distal ends through which the substance(s) can be delivered.
- One or more tubes 20 may also have a plurality of openings 24 along their lengths through which the substance(s) can be delivered.
- one or more tubes 20 can be fabricated of a material permeable or semi-permeable to the substance contained within the tubes 20 .
- each tube 20 can have one or more of the various types of delivery mechanisms and, also, it is possible to for different tubes to have different types of delivery mechanisms.
- each tube 20 can be designed to provide the optimal type of delivery based on the substance to be delivered, the location of delivery and the desired rate of delivery.
- a plurality of substances may be delivered by a single device by providing a body member 2 with a lumen 10 having impermeable dividers 25 located along the length of the lumen 10 as shown for example, in FIG. 5 a .
- the lumen 10 would contain a plurality of compartments 26 , each of which could be filled with a different substance. These compartments 26 could be filled prior to insertion through an injection port 32 located, for example, in the side of each compartment 16 as shown in FIG. 5 b .
- the device may be filled after it is implanted by providing a plurality of conduits 30 each in fluid communication with a corresponding compartment 25 .
- conduits 30 may be located within the wall of the body member 2 , along the circumference of the body member 2 , for example, as shown in FIG. 5 c .
- the substances could then be injected through a plurality of ports 34 a , 34 b , 34 c , 34 d , 34 e each in fluid communication with a corresponding conduit 30 .
- a substance could be injected into the first compartment 26 a just below the rim or cap 8 by a port 34 a in the center of the rim or cap 8 , which delivers the substance directly into the first compartment 26 a .
- a substance injected into the second port 36 b would flow through conduit 30 and would flow through an aperture in the wall of the body member 2 into second compartment 26 b , and so on.
- a delivery mechanism which may be one or more of the delivery mechanisms described above.
- substance in compartment 26 a may be delivered through one or more apertures 36 in the walls of the compartment 26 a .
- Compartment 26 b could be fabricated of a material that is permeable or semi-permeable to the substance in the compartment 26 b such that substance in compartment 26 b may be delivered by diffusion through the walls of the compartment. Such materials are set out above and may be readily determined by those in skill in the art depending on the substance in the compartment to be delivered and the desired rate of delivery of the substance.
- Substance in compartment 26 e located at the end of the non-linear body member 2 could be delivered by an exit port (not shown) located at the distal end of the compartment 26 e and, also, could be delivered by a plurality of apertures (not shown) in the walls of the compartment 26 e . In this way, each compartment may be designed for optimal delivery the particular substance housed within the compartment.
- each compartment 26 a , 26 b , 26 c , 26 d , 26 e is designed for selective “opening” or activation by a laser (via heat or photodisruption).
- a laser could be used to create apertures in the walls of the desired compartment 26 a , 26 b , 26 c , 26 d or 26 e when the particular substance is to be delivered. As such, release of each substance could be controlled upon demand by a physician.
- a pump-driven (e.g. Spring, gas-driven, nitinol, piezoelectric, osmotic) system including is coupled to the device, allowing for more sustained delivery.
- the one or more lumens 10 , 10 a can be refilled by injection into the lumen(s) 10 , 10 a themselves or through an external conduit.
- a separate pump device and reservoir housing one or more substances could be located within the eye or remotely (i.e. behind the ear subcutaneously).
- a conduit between the pump and the delivery device within the eye could run subcutaneously into the orbit, subconjunctively and through the sclera into the posterior chamber.
- the conduit must have sufficient slack to allow for ocular movements without displacing the conduit.
- the delivery device may further include a nonbiodegradable backbone (not shown) located along the non-linear body member 2 .
- a nonbiodegradable backbone (not shown) located along the non-linear body member 2 .
- one or more thin, wire-like members fabricated of a nonbiodegradable material may be located within the walls of the body member 2 or, for example, in the center of the cluster of tubes 20 shown in FIG. 4 d .
- nonbiodegradable materials are well-known and may be readily determined by one of skill in the art.
- some suitable nonbiodegradable polymers may include, for example, polymethylmethacrylate, a silicone elastomer, or silicone rubber.
- suitable non-erodible, biocompatible polymers which may be used in fabricating the body member 2 may include polyolefins such as polypropylene and polyethylene, homopolymers, and copolymers of vinyl acetate such as ethylene vinyl acetate copolymer, polyvinylchlorides, homopolymers and copolymers of acrylates such as polyethylmethacrylate, polyurethanes, polyvinylpyrrolidone, 2-pyrrolidone, polyacrylonitrile butadiene, polycarbonates, polyamides, fluoropolymers such as polytetrafluoroethylene and polyvinyl fluoride, polystyrenes, homopolymers and copolymers of styrene acrylonitrile, cellulose acetate, homopolymers and copolymers of acrylonitrile butadiene styrene, polymethylpentene, polysulfones, polyesters, polyimides, natural rubber, polyiso
- the delivery device 1 includes backbone (not shown) fabricated of a shape memory material described above.
- the body member 2 may be fabricated of any of the materials described above.
- the body member 2 is fabricated of a flexible material and a shape memory backbone located within the wall of the body member 2 or, for example, in the center of a cluster of tubes 20 shown in FIG. 4 d .
- the backbone, along with the body portion of the device is first deformed to a shape that makes it easier to insert into the eye, such as a linear shape.
- the backbone will hold the device in this deformed shape.
- the backbone, along with the body portion of the device will then return to the remembered shape.
- the dimensions of the delivery device will depend on the intended application of the device, and will be readily apparent to those having ordinary skill in the art.
- the device when the delivery device is used to deliver substances to the posterior chamber of the eye, the device is preferably designed for insertion through a small incision that requires few of no sutures for scleral closure at the conclusion of the procedure.
- the device is preferably inserted through an incision that is no more than about 1 mm in cross-section, e.g. ranging from about 0.25 mm to about 1 mm in diameter, more preferably less than 0.5 mm in diameter.
- the body member 2 When used to deliver agents to the posterior chamber of the eye, the body member 2 preferably has a length from its proximal end 4 to its distal end 6 that is less than about 1.5 cm, e.g. ranges from about 0.5 cm to about 1.5 cm such that when the rib or cap 8 abuts the outer surface of the eye, the delivery mechanism is positioned near the posterior chamber of the eye.
- the use of the delivery device of the present invention can be further understood from the following discussion relating to a method for treating chronic diseases of the eye by sustained release of therapeutic agent to the eye and with reference to FIGS. 1-6 .
- the delivery device is generally used by the following procedure: the delivery device is prepared, either empty or housing the substance to be delivered.
- an incision is made to provide access to the treatment site.
- a sclerotomy is created for insertion of the delivery device.
- Conventional techniques may be used for the creation of the sclerotomy. Such techniques require the dissection of the conjunctiva 44 and the creation of pars plana scleral incisions through the sclera 46 . As shown in FIG.
- the dissection of the conjunctiva 44 typically involves pulling back the conjunctiva 44 about the eye 42 so as to expose large areas of the sclera 46 and the clipping or securing of the conjunctiva 44 in that pulled back state (normal position of conjunctiva shown in phantom).
- the sclera 46 is not exposed only in the areas where the pars plana scleral incisions are to be made. Surgical instruments used in the procedure are then passed through these incisions.
- the incisions created for the procedure must be made large enough to accommodate the instruments required for the procedure.
- the distal end 6 may be pointed or beveled and used to create the incision.
- the creation of the sclerotomy may be accomplished by use of an alignment device and method, such as that described in U.S. Ser. No. 09/523,767, the teachings of which are incorporated herein by reference, that enables sutureless surgical methods and devices therefore.
- an alignment device and method such as that described in U.S. Ser. No. 09/523,767, the teachings of which are incorporated herein by reference, that enables sutureless surgical methods and devices therefore.
- such methods and devices do not require the use of sutures to seal the openings through which instruments are inserted.
- the alignment devices are inserted through the conjunctiva and sclera to form one or more entry apertures.
- the alignment devices are metal or polyimide cannulas through which the surgical instruments used in the procedure are inserted into the eye.
- the body member 2 is then inserted into the eye.
- the body member 2 is inserted into the eye by screwing or twisting the body member 2 into eye until the rim or cap 8 abuts the outer surface of the eye.
- the shape memory material is first cooled to a temperature at which the martensite phase is stable and the device is deformed, for example, into a linear shape. The device is then inserted into the eye. To return the device to its memory shape, the device is left unrestrained and is simply heated to a temperature above the martensite phase temperature.
- the shape memory material may be heated by a laser to return the device to a temperature above the martensite phase temperature.
- the shape memory material may also be selected such that the martensite phase temperature is below body temperature so that the material is simply cooled to below body temperature, deformed to a linear shape and inserted into the eye. Then, as the material warms up within the eye to body temperature, the device returns to its remembered shape.
- the rim or cap 8 may then be sutured or otherwise secured to the sclera to hold the delivery device in place. If a cover is used to close the port(s) 12 , 12 a it is removed at this time, and, if used, a collar for providing a snug fit about the syringe or other injection mechanism is mounted on the port(s) 12 , 12 a . The syringe or other injection mechanism is then connected to the port(s) 12 , 12 a for injection of the one ore more substances into the delivery device.
- the port(s) 12 , 12 a are composed of an injectable self-sealing material through which the needle of a syringe or other injection mechanism may be inserted and which seals off automatically when the needle other injection mechanism is removed, the needle or other injection mechanism is simply inserted through the port and the substance injected. Following injection, the conjunctiva may be adjusted to cover the rim or cap 8 of the device.
- some substances suitable for delivery to the eye may include, for example, antibiotics such as tetracycline, chlortetracycline, bacitracin, neomycin, polymyxin, gramicidin, cephalexin, oxytetracycline, chloramphenicol, rifampicin, ciprofloxacin, tobramycin, gentamycin, and erythromycin and penicillin; antifungals such as amphotericin B and miconazole; antibacterials such as sulfonamides, sulfadiazine, sulfacetamide, sulfam
- additives may further be included in the substance and, for example, some suitable additives may include water, saline, dextrose, carriers, preservatives, stabilizing agents, wetting agents, emulsifying agents or other similar materials.
- the delivery device may be refilled for further delivery or removed if the required dose of agent has been delivered for treatment of the condition.
- the invention is not be limited to ocular applications, and is particularly useful in other limited access regions such as the inner ear.
- kits that comprise one or more devices of the invention, preferably packaged in sterile condition.
- Kits of the invention also may include, for example, one or more body members 2 , means for suturing or securing the device to the sclera, etc. for use with the device, preferably packaged in sterile condition, and/or written instructions for use of the device and other components of the kit.
Abstract
An therapeutic agent delivery device that can allows is particularly suitable for delivery of a therapeutic agent to limited access regions, such as the posterior chamber of the eye and inner ear. Preferred devices of the invention are minimally invasive, refillable and may be easily fixed to the treatment area. Preferred delivery devices of the invention also include those that comprise a non-linear shaped body member body housing one or more substances and a delivery mechanism for the sustained delivery of the one or more substances from the non-linear shaped body member to the patient.
Description
- The present application claims the benefit of U.S. provisional application 60/228,934, filed Aug. 30, 2000, which is incorporated herein by reference in its entirety.
- The present invention relates to a device and method for intraocular delivery of therapeutic agents. Preferred devices of the invention include a non-linear portion that resides within a patient's eye during use that can facilitate the delivery of a therapeutic agent.
- The delivery of drugs to the eye presents many challenges. The ocular absorption of systemically administered pharmacologic agents is limited by the blood ocular barrier, namely the tight junctions of the retinal pigment epithelium and vascular endothelial cells. High systemic doses can penetrate this blood ocular barrier in relatively small amounts, but expose the patient to the risk of systemic toxicity. Topical delivery of drugs often results in limited ocular absorption due to the complex hydrophobic/hydrophilic properties of the cornea and sclera. Additionally, topical agents are mechanically removed by the blink mechanism such that only approximately 15% of a single drop is absorbed. Diffusion of topically administered drugs to the posterior chamber occurs, but often at sub-therapeutic levels. Intravitreal injection of drugs is an effective means of delivering a drug to the posterior segment in high concentrations. However, these repeated intraocular injections carry the risk of infection, hemorrhage and retinal detachment. Patients also find this procedure somewhat difficult to endure.
- Local sustained delivery of therapeutics to the posterior chamber is critical in managing several chronic diseases of the eye. To address this need, several drug delivery devices have been developed for intraocular insertion into the vitreous region of the eye.
- U.S. Pat. No. 4,300,557, for example, describes an intraocular implant in the form of a silicone capsule, which can be filled with a drug to be delivered. The implant is inserted through an incision into the vitreous region of the eye. After insertion of the implant, the incision is closed and the capsule remains in place for a period of time. Attached to the implant is a tube that passes through the surface of the eye. The tube may be used for subsequent injection of a drug while the implant is in the eye. The implant may be removed by making a second surgical incision into the eye and retrieving the implant. While in the vitreous, the device is not anchored and may move about freely. Because the overall shape of the capsule is linear, the amount of drug that may held by the device and that may be delivered over the surface area of the device is limited. If the width of the capsule is increased, excessive sized incisions will be required for insertion of the device. If the length of the capsule is increased to greater than 1 cm, the implant will pass into the central visual field of the eye, thereby causing blind spots in the patient's eye as well as increase risk of damage to the retinal tissue and lens capsule.
- U.S. Pat. No. 5,378,475 describes a device which has been developed for insertion in the vitreous region of the eye, and is described in T. J. Smith et al., Sustained-Release Ganciclovir, Arch. Ophthalmol, 110, 255-258 (1992) and G. E. Sanborn, et al., Sustained-Release Ganciclovir Therapy for Treatment of Cytomegalovirus Retinitis. Use of an Intravitreal Device, Arch. Ophthalmol, 110, 188-195 (1992). This device consists of an inner core of pharmacologic agent surrounded by two coatings with different permeabilities. Drug diffuses through a small opening in one of these coatings achieving near-order release kinetics. It is implanted in the region of the pars plana through a 3.5-5.0 mm scleral incision. The implant must be removed and replaced every 6 months in the operating room as the drug becomes depleted. There is an approximately 25% complication rate from these procedures. The device is membrane diffusion drug delivery system that relies on EVA/PVA polymers to mediate release rate. Thus, many agents cannot be effectively delivered from such a system because their permeation rate through the rate controlling material of the system is too small to produce a useful effect. Other agents cannot be satisfactorily delivered by diffusional devices because of a particular chemical characteristic of the agent. This includes salts, because of their ionic character, and unstable polar compounds that cannot be formulated into a composition suitable for storage and delivery from such systems.
- U.S. Pat. No. 5,098,443 describes certain specific implants that are inserted through incisions made in the eye wall or sutured around the globe of the eye. These rings may be formed from biodegradable polymers containing microparticles of drug. Alternatively, the implant may be in the form of a hollow flexible polymeric cocoon with the drug disposed therewithin for slow release by osmosis. No anchoring device is described.
- U.S. Pat. No. 5,466,233 describes a certain tack for intraocular drug delivery. This device has an end that is positioned in the vitreous cavity while the head remains external to the eye and abuts the scleral surface. The tack contains a fixation portion to attempt to retain attachment within the eye. Because the overall shape of the capsule is linear, the amount of drug that may held by the device and the surface area through which the drug may be delivered is limited. If the width of the capsule is increased, excessive sized incisions will be required for insertion of the device. If the length of the capsule is increased to greater than 1 cm, the implant will pass into the central visual field of the eye, thereby causing blind spots in the patient's eyes well as increase risk of damage to the retinal tissue and lens capsule.
- The present invention provides methods and devices for the intraocular delivery of substances including, for example, therapeutic agents and medicaments.
- Preferred devices of the invention have a non-linear shape during residence within a patient's eye. Preferred designs have multiple turns or angles, particularly substantially coil or helical configurations, at least for those portions that reside within a patient's eye during use.
- Preferred device of the invention also include those that have a quite small cross-section shape, at least with respect to areas that reside within a patient's eye during use. Such devices can be implanted by minimally invasive surgical procedures, including without the need for any sutures to implant or after use of the use.
- An exemplary embodiment of the delivery device includes a body member that is non-linear in shape. In one embodiment, the device has a non-linear shape before, during and after the device is inserted into the eye. In another embodiment, the device is fabricated of a “shape memory” material wherein the device is linear as it is inserted into the eye and wherein the device takes on a non-linear shape once it is implanted in the eye. Preferred shape memory materials include known materials such as, for example, shape memory alloys (SMA) like nitinol, shape memory polymers (SMP) like AB-polymer networks based on oligo(e-caprolactone) dimethacrylates and n-butyl acrylate.
- We have found the non-linear shape of the body member provides a number of advantages. The non-linear shape provides a built-in anchoring mechanism that prevents unwanted movement of the device and unwanted ejection of the device out of the eye since the non-linear shape of the body member requires manipulation of the device to get it out of an incision. For example, in a preferred embodiment, wherein the implant is in the shape of a coil, the device can be removed only by twisting the device out of the eye and, thus, is not susceptible to ejection by the eye or unwanted movement within the eye. Further, the non-linear shape geometry of the body member provides greater surface area per length of the device. This is advantageous because it is desirable to limit the length of drug delivery implants to prevent the implant from entering the central visual field (See
FIG. 6 which follows). If the implant enters the central visual field, this will result in blind spots in the patient's vision and will increase the risk of damage to the retina tissue and lens capsule. By forming the body member in a non-linear shape, the device of the present invention holds a greater volume of materials per length of the device and it also provides a larger surface area per length of the device through which the material may be delivered. - The delivery device may further include a rim or cap at its proximal end. During use, the device is inserted into the eye through an incision until the rim or cap abuts the incision. If desired, the rim or cap may then be sutured to the eye to further stabilize and prevent the device from moving once it is implanted in its desired location.
- In one embodiment, body member has a lumen extending along its length for housing the substance to be delivered. Preferably, a port in fluid communication with the lumen is located at the proximal end of the device. This allows for filling and refilling of the device after the device has been implanted in the eye. The substance in the lumen can then be delivered to the eye by a delivery mechanism. The lumen, in some embodiments, may further include a number of dividers to form a plurality of compartments each of which could be filled with a different substance, thereby allowing for delivery of more that one substances by the same device at the same time, if desired.
- In one embodiment, the delivery mechanism comprises one or more exit apertures located at the distal end of the body member. In another embodiment, the delivery mechanism comprises a plurality of openings along the body member. In another embodiment, the delivery mechanism comprises the material forming the body member. For example, the material forming the body member may be a material that is permeable or semi-permeable to the substance to be delivered. In another embodiment, the body member is fabricated of a synthetic biodegradable polymer containing microparticles of the substance to be delivered. As the polymer decomposes, the substance to be delivered is released into the eye.
- Other aspects and embodiments of the invention are discussed infra.
-
FIG. 1 illustrates transcleral placement of the delivery device in accordance with one embodiment of the present invention. -
FIG. 2 a illustrates the delivery device in accordance with one embodiment of the present invention. -
FIG. 2 b is an enlarged view of a portion of the body member of the delivery device shown inFIG. 2 a showing the lumen. -
FIG. 2 c is an enlarged cross-sectional view of the body member of the delivery device shown inFIG. 2 a. -
FIG. 3 a illustrates the delivery device having a delivery mechanism in accordance with one embodiment of the present invention. -
FIG. 3 b illustrates the delivery device having a delivery mechanism in accordance with another embodiment of the present invention. -
FIG. 3 c illustrates the delivery device having a delivery mechanism in accordance with another embodiment of the present invention. -
FIG. 4 a is an enlarged view of a portion of the body member of the delivery device in accordance with another embodiment of the present invention showing a plurality of lumen. -
FIG. 4 b is an exploded view of the cap or rim and a portion of the body member shown inFIG. 4 a showing one arrangement of a plurality of lumen. -
FIG. 4 c is an exploded view of the cap or rim and a portion of the body member shown inFIG. 4 a showing another arrangement of a plurality of lumen. -
FIG. 4 d illustrates another embodiment of the body member comprising a cluster of tubes. -
FIG. 5 a illustrates the delivery device in accordance with another embodiment of the present invention showing a lumen separated into a plurality of compartments. -
FIG. 5 b shows the delivery device ofFIG. 5 a and further shows one type of delivery mechanism in accordance with the present invention. -
FIG. 6 shows a shows a cross-sectional view of an eye illustrating the central visual field of the eye. -
FIG. 7 shows a cross-sectional schematic view of an eye illustrating one technique of pulling back of the conjunctiva to provide access into the eye for insertion of the delivery device of the present invention. - As discussed above, preferred delivery devices of the invention have a non-linear (arcuate) shape during residence within a patient's eye. Preferred designs have multiple turns or angles. For example, preferred designs the device has at least two, three, four, five, six, seven, right, nine or ten separate deviations from a linear path. A coil design is particularly preferred, although other multiple-angle configurations are also suitable such as a substantially Z-shape and the like.
- Referring now to the various figures of the drawing, wherein like reference characters refer to like parts, there is shown various views of a
delivery device 1, in accordance with the invention. - As shown in
FIGS. 1-5 c, thedelivery device 1 includes a non-linearshaped body member 2 having aproximal end 4, adistal end 6. In one preferred embodiment, thebody member 2 has a coil shape, as shown inFIGS. 1-5 c. However, the shape of thebody member 2 is not limited to a coil shape and other non-linear shapes may be used such as, for example, other random curled shapes, a zig-zag shape, a “J” shape and the like. For at least some aspects of the invention, a substantially “C” shape configuration is less preferred. - As discussed above, the non-linear shape of the
body member 2 provides a number of advantages. The large intravitreal surface area provided by the non-linear shape geometry of thebody member 2 can allow for more optimal sustained release of the substance through diffusion, enzymatic degradation, active pumping and other types of delivery. When implanted in the eye, it is desirable to limit the length “L” of drug delivery implants prevent the drug delivery implant from entering the central visual field “A” (SeeFIG. 6 ). If the implant enters the central visual field A, this will result in blind spots in the patient's vision and will increase the risk of damage to the retina tissue and lens capsule. Thus, for example, when the implant is inserted at the pars plana, the distance from the implantation site on the pars plana to the central visual field is approximately 1 cm. Thus, the overall length of the implant is preferably less than 1 cm. By providing abody member 2 that has a non-linear shape, the device of the present invention holds a greater volume of materials per length of the device without having to make the cross section of the device and, thus, the size of the insertion incision) larger, and it also provides a larger surface area per length of the device through which the material may be delivered. Still further, the non-linear shape of thebody member 2 provides a built-in anchoring system that prevents unwanted movement of the device and unwanted ejection of the device out of the eye since the non-linear shape of the body member requires manipulation of the device to get it out of an incision (e.g. a coil-shapedbody member 2 would require twisting the device out of the eye, and a zig-zag shapedbody member 2 would require moving the device back and forth to remove the device from the eye). - In one preferred embodiment, the delivery device has a coil-shaped
body member 2 as shown inFIGS. 1-5 c. The coil shape of the device provides a large intravitreal surface area through which material can be delivered. Further, the coil shape of the body member allows the device to be screwed or twisted into the eye through an incision approximately the same size as the outer diameter of the tube forming thebody member 2. Still further, the coil shape of the body member acts as an anchoring mechanism that holds thedelivery device 1 within the eye and prevents unwanted movement of the delivery device and unwanted ejection of thedelivery device 1 out of the eye. Due to the coil shape, thedelivery device 1 must be twisted and unscrewed out of the eye. - In general, the materials used in fabricating the
body member 2 are not particularly limited, provided these materials are biocompatible. Preferably, these materials are also insoluble in the body fluids and tissues that the device comes into contact with. It is further preferred that thebody member 2 is fabricated of a flexible material so that small movements of the delivery device will not be translated to the retina, thereby minimizing the risk of retinal tearing, detachment and other damage. In some embodiments, as described in further detail below, it is preferable that at least thedistal end 6 ofbody member 2 is fabricated of a rigid, non-pliable material. In some embodiments, as described in further detail below, it is preferable that at least a portion of the material used to form thebody member 2 is permeable or semi-permeable to the substance to be delivered. In some embodiments, as set out above, it is preferable that the body member is fabricated of a material having shape memory and/or superelastic characteristics. - In one embodiment, the
body member 2 is fabricated of a nonbiodegradable polymer. Such nonbiodegradable polymers are well-known and may include, for example, polymethylmethacrylate, a silicone elastomer, or silicone rubber. Other suitable non-erodible, biocompatible polymers which may be used in fabricating thebody member 2 may include polyolefins such as polypropylene and polyethylene, homopolymers, and copolymers of vinyl acetate such as ethylene vinyl acetate copolymer, polyvinylchlorides, homopolymers and copolymers of acrylates such as polyethylmethacrylate, polyurethanes, polyvinylpyrrolidone, 2-pyrrolidone, polyacrylonitrile butadiene, polycarbonates, polyamides, fluoropolymers such as polytetrafluoroethylene and polyvinyl fluoride, polystyrenes, homopolymers and copolymers of styrene acrylonitrile, cellulose acetate, homopolymers and copolymers of acrylonitrile butadiene styrene, polymethylpentene, polysulfones, polyesters, polyimides, natural rubber, polyisobutylene, polymethylstyrene and other similar non-erodible biocompatible polymers. - The
body member 2 of thedelivery device 1 can, in one embodiment, have a non-linear shape prior to, during and after insertion of the device into the eye. Alternatively, thedelivery device 1 can be fabricated of a material having shape memory and/or superelastic characteristics that allows the device to be deformed and made, for example, linear, for easier insertion into the eye and which returns to its original shape after it is inserted into the eye. In this embodiment, thedelivery device 1 has a “memory shape” that it will take on under certain conditions. For example, thedelivery device 1 may have a zig-zag or coiled memory shape. Then, when the surgeon wishes to implant the device into the eye, the surgeon may deform thedelivery device 1 into a linear shape for quick and easy insertion of the device through an incision the size of the cross section of the linear shaped device. Upon insertion of thedelivery device 1, the device can then take on its zig-zag, coiled or other memory shape. - Materials having shape memory and/or superelastic characteristics are well-known and may include any materials known in the art such as, for example, shape memory alloys (SMA) like nitinol (Ni—Ti alloy) and shape memory polymers (SMP) like AB-polymer networks based on oligo(e-caprolactone) dimethacrylates and n-butyl acrylate. Shape memory alloys generally have at least two phases: (1) a martensite phase, which has a relatively low tensile strength and which is stable at relatively low temperatures, and (2) an austenite phase, which has a relatively high tensile strength and which is stable at temperatures higher than the martensite phase. The shape memory characteristics are imparted on the material by heating the material to a temperature above the temperature at which the austenite phase is stable. While the material is heated to this temperature, the device is held in the “memory shape”, which is shape that is desired to be “remembered”. Such materials and methods of imparting shape memory characteristics are further described in, for example, U.S. Pat. No. 4,665,905, U.S. Pat. No. 4,925,445 and U.S. Pat. No. 6,245,100.
- Preferably, the delivery device of the present invention takes advantage of the superelastic properties of the material to extend the device into a linear shape. Once injected into the eye in an unconstrained form, the device will retain its memory shape.
- The
distal end 6 of thebody member 2 may be blunt or, in some embodiments, it is pointed or has a beveled ramp-like configuration so that thedistal end 6 may be used to pierce the eye during insertion. In one embodiment, thedistal end 6 has a ramp-like angle of about 30°. If thedistal end 6 of thebody member 2 is used to pierce the eye during insertion, at least thedistal end 6 is fabricated of a rigid, non-pliable material suitable for piercing the eye. Such materials are well known and may include, for example, polyimide and similar materials. - As shown in
FIGS. 1, 2 a, 3 a-c and 5 a-c, a rim orcap 8 may further be located at theproximal end 4 of thebody member 2 to assist in stabilizing thedevice 1 once implanted in the eye. Preferably, thedelivery device 1 is inserted into the eye through an incision until the rim orcap 8 abuts the incision. If desired, the rim orcap 8 may then be sutured to the eye to further stabilize and prevent the device from moving once it is implanted in its desired location. - The overall size and shape of the rim or
cap 8 is not particularly limited provided that irritation to the eye is limited. For example, while the rim orcap 8 is shown circular in shape, the rim or cap may be of any shape, for example, circular, rectangular, triangular, etc. However, to minimize irritation to the eye, the rim orcap 8 preferably has rounded edges. Further, the rim orcap 8 is designed such that it remains outside the eye and, as such, the rim orcap 8 is sized so that it will not pass into the eye through the opening in the eye through which the device is inserted. The rim orcap 8 may further be designed such that it can be easily sutured or otherwise secured to the surface surrounding the opening in the eye and may, for example, contain a plurality of holes (not shown) through which sutures may pass. - The materials used in fabricating the rim or
cap 8 are not particularly limited, provided these materials are biocompatible and preferably insoluble in the body fluids and tissues that the device comes into contact with. Further, it is preferred that the rim orcap 8 is fabricated of a material that does not cause irritation to the portion of the eye that it contacts. As such, preferred materials are pliable and may include, by way of example, various polymers including, for example, silicone elastomers and rubbers, polyolefins, polyurethanes, acrylates, polycarbonates, polyamides, polyimides, polyesters, and polysulfones. - In one embodiment, as shown in
FIGS. 2 a-4 c and 5 a-5 c, thenon-linear body member 2 is fabricated of a tube that is wound into a coiled shape. As shown in the Figures, the tube forming thenon-linear body member 2 is preferably cylindrical in shape, with a circular cross-section. However, the shape of the tube is not limited and, for example, may alternatively have square, rectangular, octagonal or other cross-sectional shapes. Preferably, the tube has alumen 10 extending along its length for housing the substance to be delivered. In one embodiment, thelumen 10 is filled with the substance prior to inserting the device into the eye. Alternatively, thelumen 10 may be filled with the substance after the delivery device has been inserted into the eye. This may be accomplished by providing aport 12 near theproximal end 4 of thebody member 2 in fluid communication with thelumen 10. This further allows for refilling of the device during use, if required. - In one embodiment, the
port 12 is preferably designed such that the needle of a syringe, or similar injection mechanism, may be inserted into theport 12 and the substance injected by the syringe or injection mechanism. Thus, the substance travels through theport 12 and into thelumen 10. Theport 12 preferably forms a snug seal about the needle of the syringe or injection mechanism to prevent leakage of the substance out of theport 12 around the syringe needle or injection mechanism and to provide sterile injection of agent into thelumen 10. If desired, fittings or collars (not shown), through which a syringe needle or injection mechanism may be inserted and which form a snug seal about the syringe needle or injection mechanism, may be mounted on theport 12. Upon injection of the substance into the delivery device, the needle of the syringe or the injection mechanism is removed from theport 12 and theport 12 sealed. This may be accomplished by providing a removable cover (not shown) on theport 12 that may be removed for injection of the substance and replaced when the substance has been injected. In a preferred embodiment, theport 12 is fabricated of an injectable self-sealing material through which the needle or injection mechanism may be inserted and which seals off automatically when the needle or injection mechanism is removed. Such materials are known and include, for example, silicone rubber, silicone elastomers and polyolefin. - Once the device is implanted in the desired location and the substance is housed within the
lumen 10, the substance can then be delivered to the eye by a delivery mechanism. - In one embodiment, as shown in
FIG. 3 a, the delivery mechanism comprises anexit aperture 16 located at thedistal end 6 of thebody member 2. Alternatively, as shown inFIG. 3 b, a plurality ofexit apertures 16 a located at thedistal end 6 of thebody member 2 may form the delivery mechanism. The number and size of the one ormore exit apertures 16 may vary depending on the desired rate of delivery of the agent and may be readily determined by one of skill in the art. The one ormore exit apertures 16 are designed such that the substance is slowly diffused rather than expelled as a fluid stream, which may damage the delicate tissues of the eye. For example, in one embodiment, this may be achieved by, for example, placing a covering or lining (not shown) over thedistal exit aperture 16, wherein the covering or lining has a particular porosity to the agent or wherein the covering or lining is fabricated of a diffusion or rate-limiting membrane, matrix material or similar material. - In another embodiment, for example, as shown in
FIG. 3 c, the delivery mechanism comprises a plurality ofopenings 18 along thebody member 2. The number and size of the one ormore openings 18 may vary depending on the desired rate of delivery of the agent and may be readily determined by one of skill in the art. Further, the location of the plurality ofopenings 18 may be situated so as to deliver the substance at a particular location once the device is implanted in the eye. The plurality ofopenings 18 are designed such that the substance is slowly diffused rather than expelled as a fluid stream, which may damage the delicate tissues of the eye. In this embodiment, anexit aperture 16 at thedistal end 6 of thebody member 2 as described above may also be included. - In another embodiment, the delivery mechanism comprises the material forming the
body member 2. For example, the material forming thebody member 2 may be a material that is permeable or semi-permeable to the substance to be delivered. Such materials may vary depending on the particular application and the substance to be delivered and may be readily determined by one of skill in the art. By way of example, some suitable permeable materials may include polycarbonates, polyolefins, polyurethanes, copolymers of acrylonitrile, copolymers of polyvinyl chloride, polyamides, polysulphones, polystyrenes, polyvinyl fluorides, polyvinyl alcohols, polyvinyl esters, polyvinyl butyrate, polyvinyl acetate, polyvinylidene chlorides, polyvinylidene fluorides, polyimides, polyisoprene, polyisobutylene, polybutadiene, polyethylene, polyethers, polytetrafluoroethylene, polychloroethers, polymethylmethacrylate, polybutylmethacrylate, polyvinyl acetate, nylons, cellulose, gelatin, silicone rubbers and porous rubbers. - The particular material used to fabricate the
body member 2 may be chosen to provide a particular rate of delivery of the substance, which may be readily determined by one of skill in the art. Further, the rate of delivery of the substance may also be increased or decreased by varying the percentage of thebody member 2 formed of the material permeable to the agent. Thus, for example, to provide a slower rate of delivery, thebody member 2 may be fabricated of 50% or less permeable material. For example, thebody member 2 may be fabricated of 1%, 5%, 10%, 20%, 30%, 40% or 50% of permeable material. For a faster rate of delivery, thebody member 2 may be fabricated of greater than 50% of permeable material. For example, thebody member 2 may be fabricated of 51%, 55%, 60%, 70%, 80%, 90% or 100% of permeable material. When one or more portions of thebody member 2, rather than thewhole body member 2, is fabricated of a permeable or semi-permeable material, the location of the permeable or semi-permeable material may be situated so as to deliver the substance at a particular location once the device is implanted in the eye. - In another embodiment, the
body member 2 is fabricated of a synthetic biodegradable polymer containing microparticles of the substance to be delivered. Thus, in this embodiment, as the polymer decomposes, the substance to be delivered is released into the eye. Release time is a function of the polymer and the shape and size of thebody member 2 and may be readily determined by one of ordinary skill in the art. Such biodegradable polymers may vary depending on the particular application and may be readily determined by one of skill in the art. By way of example, some suitable biodegradable polymers may include polyesters of molecular weight from about 4,000 to about 100,000, homopolymers and copolymers of polylactic acid and polyglycolic acid, polycaprolactone, homopolymers and copolymers of polyanhydrides such as terephthalic acid anhydride, bis(p-anhydride) and poly(p-carboxyphenoxy) alkyl, homopolymers and copolymers of dicarboxylic acids such as sebacic, adipic, oxalic, phthalic and maleic acid, polymeric fatty acid dimer compounds such as polydodecanedioic acid polyorthoesters, poly(alkyl-2-cyanoacrylate) such as poly(hexyl-2-cyanoacrylate), collagen (gelatin), polyacetals, divinyloxyalkylenes, polydihydropyrans, polyphosphazenes, homopolymers and copolymers of amino acids such as copolymers of leucine and methyl glutamate, polydioxinones, polyalkylcyano acetates, polysaccarides and their derivatives such as dextran and cyclodextran, cellulose and hydroxymethyl cellulose. - In another embodiment, rather than a
single lumen 10, thenon-linear body member 2 includes a plurality oflumens 10 a capable of housing and delivering a plurality of substances. Thus, for example, eachlumen 10 a may be in fluid communication with plurality ofports 12 a. Theseports 12 a are similar to thesingle port 12 described above. (e.g. theports 12 a may include a cover that may be removed for injection of the substance and replaced when the substance has been injected, or theports 12 a may be fabricated of an injectable self-sealing material) If desired, thelumens 10 a andports 12 a may be arranged such that eachlumen 10 a may be filled with a different substance through the correspondingports 12 a. Thus, the single device may be used to deliver more than one substance if desired. - In one embodiment, the plurality of
lumens 10 a are situated in a ring about the outer circumference of thebody member 2 as shown inFIG. 4 b. The substance(s) may be injected into thelumens 10 a for delivery through a delivery mechanism, which may be any of the delivery mechanisms described above or a combination of the delivery mechanisms described above. - In another embodiment, a plurality of
lumen 10 a are clustered within thebody member 2 as shown inFIG. 4 c. The substance(s) may be injected into thelumens 10 a for delivery through a delivery mechanism. In this embodiment, theinner lumens 10 a preferably deliver their housed substances through one ormore apertures distal end 6 of thebody member 2, while theouter lumens 10 a located at the outer circumference of thebody member 2 may deliver their housed substances through one ormore apertures distal end 6 of thebody member 2, a plurality ofopenings 18 along thebody member 2, and/or through the material forming thebody member 2 as described above. - In yet another embodiment, the
non-linear body member 2 is formed of a plurality oftubes 20 clustered and wound into a coil shape as shown inFIG. 4 d. In this embodiment, the substance(s) to be delivered is/are inserted into and housed within the plurality ofhollow tubes 20. The plurality oftubes 20 may contain different substances or the same substance as desired. The substances are then delivered by one or more of the delivery mechanisms set out above. For example, in one embodiment, one or more of thetubes 20 may have one ormore exit apertures 22 at their distal ends through which the substance(s) can be delivered. One ormore tubes 20 may also have a plurality of openings 24 along their lengths through which the substance(s) can be delivered. Still further, one ormore tubes 20 can be fabricated of a material permeable or semi-permeable to the substance contained within thetubes 20. Thus, it is possible for eachtube 20 to have one or more of the various types of delivery mechanisms and, also, it is possible to for different tubes to have different types of delivery mechanisms. In this way, eachtube 20 can be designed to provide the optimal type of delivery based on the substance to be delivered, the location of delivery and the desired rate of delivery. - In another embodiment, a plurality of substances may be delivered by a single device by providing a
body member 2 with alumen 10 havingimpermeable dividers 25 located along the length of thelumen 10 as shown for example, inFIG. 5 a. Thus, thelumen 10 would contain a plurality ofcompartments 26, each of which could be filled with a different substance. Thesecompartments 26 could be filled prior to insertion through aninjection port 32 located, for example, in the side of eachcompartment 16 as shown inFIG. 5 b. In another embodiment, the device may be filled after it is implanted by providing a plurality ofconduits 30 each in fluid communication with acorresponding compartment 25. Theseconduits 30 may be located within the wall of thebody member 2, along the circumference of thebody member 2, for example, as shown inFIG. 5 c. The substances could then be injected through a plurality ofports corresponding conduit 30. Thus, a substance could be injected into thefirst compartment 26 a just below the rim orcap 8 by aport 34 a in the center of the rim orcap 8, which delivers the substance directly into thefirst compartment 26 a. A substance injected into the second port 36 b, would flow throughconduit 30 and would flow through an aperture in the wall of thebody member 2 intosecond compartment 26 b, and so on. - The substance injected into each of the
compartments compartment 26 a may be delivered through one ormore apertures 36 in the walls of thecompartment 26 a.Compartment 26 b could be fabricated of a material that is permeable or semi-permeable to the substance in thecompartment 26 b such that substance incompartment 26 b may be delivered by diffusion through the walls of the compartment. Such materials are set out above and may be readily determined by those in skill in the art depending on the substance in the compartment to be delivered and the desired rate of delivery of the substance. Substance in compartment 26 e, located at the end of thenon-linear body member 2 could be delivered by an exit port (not shown) located at the distal end of the compartment 26 e and, also, could be delivered by a plurality of apertures (not shown) in the walls of the compartment 26 e. In this way, each compartment may be designed for optimal delivery the particular substance housed within the compartment. - In another embodiment, each
compartment compartment - In yet another embodiment, a pump-driven (e.g. Spring, gas-driven, nitinol, piezoelectric, osmotic) system (not shown) including is coupled to the device, allowing for more sustained delivery. In this embodiment, the one or
more lumens - For added structural support, the delivery device may further include a nonbiodegradable backbone (not shown) located along the
non-linear body member 2. For example, in one embodiment, one or more thin, wire-like members fabricated of a nonbiodegradable material, may be located within the walls of thebody member 2 or, for example, in the center of the cluster oftubes 20 shown inFIG. 4 d. Such nonbiodegradable materials are well-known and may be readily determined by one of skill in the art. By way of example, some suitable nonbiodegradable polymers may include, for example, polymethylmethacrylate, a silicone elastomer, or silicone rubber. Other suitable non-erodible, biocompatible polymers which may be used in fabricating thebody member 2 may include polyolefins such as polypropylene and polyethylene, homopolymers, and copolymers of vinyl acetate such as ethylene vinyl acetate copolymer, polyvinylchlorides, homopolymers and copolymers of acrylates such as polyethylmethacrylate, polyurethanes, polyvinylpyrrolidone, 2-pyrrolidone, polyacrylonitrile butadiene, polycarbonates, polyamides, fluoropolymers such as polytetrafluoroethylene and polyvinyl fluoride, polystyrenes, homopolymers and copolymers of styrene acrylonitrile, cellulose acetate, homopolymers and copolymers of acrylonitrile butadiene styrene, polymethylpentene, polysulfones, polyesters, polyimides, natural rubber, polyisobutylene, polymethylstyrene and other similar non-erodible biocompatible polymers. - In another embodiment, the
delivery device 1 includes backbone (not shown) fabricated of a shape memory material described above. In this embodiment, for example, thebody member 2 may be fabricated of any of the materials described above. In one embodiment, for example, thebody member 2 is fabricated of a flexible material and a shape memory backbone located within the wall of thebody member 2 or, for example, in the center of a cluster oftubes 20 shown inFIG. 4 d. Thus, the backbone, along with the body portion of the device, is first deformed to a shape that makes it easier to insert into the eye, such as a linear shape. The backbone will hold the device in this deformed shape. After the device is inserted into the eye, the backbone, along with the body portion of the device, will then return to the remembered shape. - The dimensions of the delivery device will depend on the intended application of the device, and will be readily apparent to those having ordinary skill in the art. By way of example, when the delivery device is used to deliver substances to the posterior chamber of the eye, the device is preferably designed for insertion through a small incision that requires few of no sutures for scleral closure at the conclusion of the procedure. As such, the device is preferably inserted through an incision that is no more than about 1 mm in cross-section, e.g. ranging from about 0.25 mm to about 1 mm in diameter, more preferably less than 0.5 mm in diameter. As such, the cross-section of the tube forming the
body member 2, or the cluster oftubes 20 as shown inFIG. 4 d, is preferably no more than about 1 mm, e.g. preferably ranging from about 0.25 mm to about 1 mm in diameter, and, more preferably, is no greater than 0.5 mm. If the tube forming thebody member 2 is not cylindrical, the largest dimension of the cross section can be used to approximate the diameter for this purpose. When used to deliver agents to the posterior chamber of the eye, thebody member 2 preferably has a length from itsproximal end 4 to itsdistal end 6 that is less than about 1.5 cm, e.g. ranges from about 0.5 cm to about 1.5 cm such that when the rib orcap 8 abuts the outer surface of the eye, the delivery mechanism is positioned near the posterior chamber of the eye. - The use of the delivery device of the present invention can be further understood from the following discussion relating to a method for treating chronic diseases of the eye by sustained release of therapeutic agent to the eye and with reference to
FIGS. 1-6 . - The delivery device is generally used by the following procedure: the delivery device is prepared, either empty or housing the substance to be delivered.
- In one embodiment, an incision is made to provide access to the treatment site. For example, when used to deliver therapeutic agent to the posterior chamber of the eye, a sclerotomy is created for insertion of the delivery device. Conventional techniques may be used for the creation of the sclerotomy. Such techniques require the dissection of the
conjunctiva 44 and the creation of pars plana scleral incisions through thesclera 46. As shown inFIG. 6 , the dissection of theconjunctiva 44 typically involves pulling back theconjunctiva 44 about the eye 42 so as to expose large areas of thesclera 46 and the clipping or securing of theconjunctiva 44 in that pulled back state (normal position of conjunctiva shown in phantom). In other words, thesclera 46 is not exposed only in the areas where the pars plana scleral incisions are to be made. Surgical instruments used in the procedure are then passed through these incisions. Thus, the incisions created for the procedure must be made large enough to accommodate the instruments required for the procedure. Alternatively, during this procedure, rather than making an incision through which the device is inserted, thedistal end 6 may be pointed or beveled and used to create the incision. - Alternatively, the creation of the sclerotomy may be accomplished by use of an alignment device and method, such as that described in U.S. Ser. No. 09/523,767, the teachings of which are incorporated herein by reference, that enables sutureless surgical methods and devices therefore. In particular, such methods and devices do not require the use of sutures to seal the openings through which instruments are inserted. The alignment devices are inserted through the conjunctiva and sclera to form one or more entry apertures. Preferably, the alignment devices are metal or polyimide cannulas through which the surgical instruments used in the procedure are inserted into the eye.
- The
body member 2 is then inserted into the eye. For example, in embodiments wherein thebody member 2 has a coiled shape, thebody member 2 is inserted into the eye by screwing or twisting thebody member 2 into eye until the rim orcap 8 abuts the outer surface of the eye. In embodiments wherein thebody member 2 or a backbone of the body member is fabricated of a shape memory material, the shape memory material is first cooled to a temperature at which the martensite phase is stable and the device is deformed, for example, into a linear shape. The device is then inserted into the eye. To return the device to its memory shape, the device is left unrestrained and is simply heated to a temperature above the martensite phase temperature. For example, the shape memory material may be heated by a laser to return the device to a temperature above the martensite phase temperature. The shape memory material may also be selected such that the martensite phase temperature is below body temperature so that the material is simply cooled to below body temperature, deformed to a linear shape and inserted into the eye. Then, as the material warms up within the eye to body temperature, the device returns to its remembered shape. - After the device is inserted into the eye, the rim or
cap 8 may then be sutured or otherwise secured to the sclera to hold the delivery device in place. If a cover is used to close the port(s) 12, 12 a it is removed at this time, and, if used, a collar for providing a snug fit about the syringe or other injection mechanism is mounted on the port(s) 12, 12 a. The syringe or other injection mechanism is then connected to the port(s) 12, 12 a for injection of the one ore more substances into the delivery device. If the port(s) 12, 12 a are composed of an injectable self-sealing material through which the needle of a syringe or other injection mechanism may be inserted and which seals off automatically when the needle other injection mechanism is removed, the needle or other injection mechanism is simply inserted through the port and the substance injected. Following injection, the conjunctiva may be adjusted to cover the rim orcap 8 of the device. - When the device is used to deliver agents to the eye for the treatment of a variety of ocular conditions such as, for example, retinal detachment, occlusions, proliferative retinopathy, diabetic retinopathy, inflammations such as uveitis, choroiditis and retinitis, degenerative disease, vascular diseases and various tumors including neoplasms, some substances suitable for delivery to the eye may include, for example, antibiotics such as tetracycline, chlortetracycline, bacitracin, neomycin, polymyxin, gramicidin, cephalexin, oxytetracycline, chloramphenicol, rifampicin, ciprofloxacin, tobramycin, gentamycin, and erythromycin and penicillin; antifungals such as amphotericin B and miconazole; antibacterials such as sulfonamides, sulfadiazine, sulfacetamide, sulfamethizole and sulfisoxazole, nitrofurazone and sodium propionate; antivirals, such as idoxuridine trifluorotymidine, acyclovir, ganciclovir and interferon; antibacterial agents such as nitrofurazone and sodium propionate; antiallergenics such as sodium cromoglycate, antazoline, methapyriline, chlorpheniramine, cetirizine, pyrilamine and prophenpyridamine; anti-inflammatories such as hydrocortisone, hydrocortisone acetate, dexamethasone 21-phosphate, fluocinolone, medrysone, methylprednisolone, prednisolone 21-phosphate, prednisolone acetate, fluoromethalone, betamethasone and triamcinolone; non-steroidal anti-inflammatories such as salicylate, indomethacin, ibuprofen, diclofenac, flurbiprofen and piroxicam; decongestants such as phenylephrine, naphazoline and tetrahydrozoline; decongestants such as phenylephrine, naphazo line, and tetrahydrazoline; miotics and anti-cholinesterase such as pilocarpine, salicylate, carbachol, acetylcholine chloride, physostigmine, eserine, diisopropyl fluorophosphate, phospholine iodine, and demecarium bromide; mydriatics such as atropine sulfate, cyclopentolate, homatropine, scopolamine, tropicamide, eucatropine, and hydroxyamphetamine; sympathomimetics such as epinephrine; antineoplastics such as carmustine, cisplatin and fluorouracil; immunological drugs such as vaccines and immune stimulants; hormonal agents such as estrogens, estradiol, progestational, progesterone, insulin, calcitonin, parathyroid hormone and peptide and vasopressin hypothalamus releasing factor; beta adrenergic blockers such as timolol maleate, levobunolol HCl and betaxolol HCl; growth factors such as epidermal growth factor, fibroblast growth factor, platelet derived growth factor, transforming growth factor beta, somatotropin and fibronectin; carbonic anhydrase inhibitors such as dichlorophenamide, acetazolamide and methazolamide; inhibitors of angiogenesis such as angiostatin, anecortave acetate, thrombospondin, and anti-VEGF antibody; and other therapeutic agents such as prostaglandins, antiprostaglandins and prostaglandin precursors.
- In some applications, additives may further be included in the substance and, for example, some suitable additives may include water, saline, dextrose, carriers, preservatives, stabilizing agents, wetting agents, emulsifying agents or other similar materials.
- Once the therapeutic agent had been delivered to the treatment area, the delivery device may be refilled for further delivery or removed if the required dose of agent has been delivered for treatment of the condition.
- The invention is not be limited to ocular applications, and is particularly useful in other limited access regions such as the inner ear.
- The present invention also includes kits that comprise one or more devices of the invention, preferably packaged in sterile condition. Kits of the invention also may include, for example, one or
more body members 2, means for suturing or securing the device to the sclera, etc. for use with the device, preferably packaged in sterile condition, and/or written instructions for use of the device and other components of the kit. - All documents mentioned herein are incorporated by reference herein in their entirety.
- The foregoing description of the invention is merely illustrative thereof, and it is understood that variations and modifications can be effected without departing from the scope or spirit of the invention as set forth in the following claims.
Claims (25)
1-67. (cancelled)
68. A drug delivery device comprising:
a non-linear shaped body member having at least two deviations from a linear and that has a shape other than a substantially C-configuration and that is implanted within a patient during use of the device to deliver a drug substance to the patient via the body member.
69. The device of claim 68 wherein the device body member comprises at least three deviations from a linear path.
70. The device of claim 68 wherein the device body member comprises at least four deviations from a linear path.
71. The device of claim 68 wherein the device body member comprises at least five deviations from a linear path.
72. The device of claim 68 wherein the device body member comprises a helical shape.
73. The device of claim 68 wherein the device body member comprises a substantially Z-shape.
74. The device of claim 68 wherein the device comprises a therapeutic agent for delivery to the patient during use of the device.
75. The device of claim 68 wherein the device body member comprises a polymer.
76. The device of claim 68 wherein the device length is about 1.5 cm or less.
77. A drug delivery device comprising:
a coil-shaped body member that is implanted in a patient during use of the device to deliver a drug substance to the patient via the body member.
78. The device of claim 77 wherein the device comprises a therapeutic agent for delivery to the patient during use of the device.
79. The device of claim 77 wherein the device body member comprises a polymer.
80. The device of claim 77 wherein the device body member comprises a polymer that comprises a therapeutic substance to be delivered to the patient.
81. The device of claim 77 wherein the device length is about 1.5 cm or less.
82. A method for treating a patient comprising:
(a) providing a delivery device comprising a non-linear shaped body member having at least two deviations from a linear path and that has a shape other than a substantially C-configuration; and
(b) inserting into a patient ear the device whereby the body member resides in the patient ear and a therapeutic substance is administered to the patient via the body member.
83. The method of claim 82 wherein the device body member comprises at least three deviations from a linear path.
84. The method of claim 82 wherein the device body member comprises at least four deviations from a linear path.
85. The method of claim 82 wherein the device body member comprises at least five deviations from a linear path.
86. The method of claim 82 wherein the device body member comprises a helical shape.
87. The method of claim 82 wherein the device body member comprises a substantially Z-shape.
88. The method of claim 82 wherein the device body member comprises a polymer.
89. The method of claim 82 wherein the device body member comprises a polymer that comprises a therapeutic substance to be delivered to the patient.
90. The method of claim 82 wherein the device comprises a shape memory material.
91. The method of claim 82 wherein the device length is about 1.5 cm or less.
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Cited By (41)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20060110428A1 (en) * | 2004-07-02 | 2006-05-25 | Eugene Dejuan | Methods and devices for the treatment of ocular conditions |
US20060134168A1 (en) * | 2004-12-07 | 2006-06-22 | Chappa Ralph A | Coatings with crystallized active agent(s) and methods |
US20060257451A1 (en) * | 2005-04-08 | 2006-11-16 | Varner Signe E | Sustained release implants and methods for subretinal delivery of bioactive agents to treat or prevent retinal disease |
WO2006125106A1 (en) * | 2005-05-18 | 2006-11-23 | Surmodics, Inc. | Insertion instrument for non-linear medical devices |
WO2007040557A1 (en) | 2005-09-21 | 2007-04-12 | Surmodics, Inc. | Coatings and articles including natural biodegradable polysaccharides |
US20070128343A1 (en) * | 2005-11-15 | 2007-06-07 | Chappa Ralph A | Apparatus And Methods for Applying Coatings |
US20080020045A1 (en) * | 2006-06-28 | 2008-01-24 | Chappa Ralph A | Combination Degradable and Non-Degradable Matrices for Active Agent Delivery |
US20080075779A1 (en) * | 2006-09-27 | 2008-03-27 | Chappa Ralph A | Additives And Methods For Enhancing Active Agent Elution Kinetics |
US20080171087A1 (en) * | 2006-08-16 | 2008-07-17 | Chappa Ralph A | Methods and materials for increasing the adhesion of elution control matrices to substrates |
US20090186059A1 (en) * | 2008-01-14 | 2009-07-23 | Johnson Elizabeth E | Devices and methods for elution of nucleic acid delivery complexes |
US20090263449A1 (en) * | 2008-04-09 | 2009-10-22 | Surmodics, Inc. | Delivery of nucleic acid complexes from materials including negatively charged groups |
US20090280181A1 (en) * | 2008-05-07 | 2009-11-12 | Joram Slager | Delivery of nucleic acid complexes from particles |
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US20110008526A1 (en) * | 2006-09-25 | 2011-01-13 | Surmodics, Inc. | Multi-layered coatings and methods for controlling elution of active agents |
US20110166555A1 (en) * | 2009-09-30 | 2011-07-07 | Jianbo Zhou | Carrier for an insertable medical device, insertion tools, methods of use, and kits |
US20110207987A1 (en) * | 2009-11-02 | 2011-08-25 | Salutaris Medical Devices, Inc. | Methods And Devices For Delivering Appropriate Minimally-Invasive Extraocular Radiation |
WO2012058274A2 (en) | 2010-10-26 | 2012-05-03 | Surmodics, Inc. | Coatings and methods for controlled elution of hydrophilic active agents |
USD691267S1 (en) | 2009-01-07 | 2013-10-08 | Salutaris Medical Devices, Inc. | Fixed-shape cannula for posterior delivery of radiation to eye |
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US8602959B1 (en) | 2010-05-21 | 2013-12-10 | Robert Park | Methods and devices for delivery of radiation to the posterior portion of the eye |
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US8663673B2 (en) | 2005-07-29 | 2014-03-04 | Surmodics, Inc. | Devices, articles, coatings, and methods for controlled active agent release or hemocompatibility |
US8901092B2 (en) | 2010-12-29 | 2014-12-02 | Surmodics, Inc. | Functionalized polysaccharides for active agent delivery |
US9056201B1 (en) | 2008-01-07 | 2015-06-16 | Salutaris Medical Devices, Inc. | Methods and devices for minimally-invasive delivery of radiation to the eye |
US9308355B2 (en) | 2012-06-01 | 2016-04-12 | Surmodies, Inc. | Apparatus and methods for coating medical devices |
US9827401B2 (en) | 2012-06-01 | 2017-11-28 | Surmodics, Inc. | Apparatus and methods for coating medical devices |
US9873001B2 (en) | 2008-01-07 | 2018-01-23 | Salutaris Medical Devices, Inc. | Methods and devices for minimally-invasive delivery of radiation to the eye |
USD808528S1 (en) | 2016-08-31 | 2018-01-23 | Salutaris Medical Devices, Inc. | Holder for a brachytherapy device |
USD808529S1 (en) | 2016-08-31 | 2018-01-23 | Salutaris Medical Devices, Inc. | Holder for a brachytherapy device |
USD814638S1 (en) | 2016-05-11 | 2018-04-03 | Salutaris Medical Devices, Inc. | Brachytherapy device |
USD814637S1 (en) | 2016-05-11 | 2018-04-03 | Salutaris Medical Devices, Inc. | Brachytherapy device |
USD815285S1 (en) | 2016-05-11 | 2018-04-10 | Salutaris Medical Devices, Inc. | Brachytherapy device |
US10022558B1 (en) | 2008-01-07 | 2018-07-17 | Salutaris Medical Devices, Inc. | Methods and devices for minimally-invasive delivery of radiation to the eye |
CN109431678A (en) * | 2018-12-17 | 2019-03-08 | 中国医学科学院北京协和医院 | Through sclerocorneal drug delivery system |
US11090468B2 (en) | 2012-10-25 | 2021-08-17 | Surmodics, Inc. | Apparatus and methods for coating medical devices |
US11628466B2 (en) | 2018-11-29 | 2023-04-18 | Surmodics, Inc. | Apparatus and methods for coating medical devices |
US11819590B2 (en) | 2019-05-13 | 2023-11-21 | Surmodics, Inc. | Apparatus and methods for coating medical devices |
US11865283B2 (en) | 2021-01-22 | 2024-01-09 | Shifamed Holdings, Llc | Adjustable shunting systems with plate assemblies, and associated systems and methods |
Families Citing this family (254)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TW586934B (en) * | 1997-05-19 | 2004-05-11 | Sumitomo Pharma | Immunopotentiating composition |
US9295581B2 (en) * | 1999-01-05 | 2016-03-29 | Second Sight Medical Products, Inc. | Medical tack with a variable effective length |
US6416777B1 (en) * | 1999-10-21 | 2002-07-09 | Alcon Universal Ltd. | Ophthalmic drug delivery device |
US7943162B2 (en) * | 1999-10-21 | 2011-05-17 | Alcon, Inc. | Drug delivery device |
DE60135352D1 (en) * | 2000-08-30 | 2008-09-25 | Univ Johns Hopkins | DEVICE FOR INTRA-OCCULAR ACTIVE AGGREGATION |
JP4657577B2 (en) * | 2001-01-09 | 2011-03-23 | マイクロチップス・インコーポレーテッド | Flexible microchip device for ocular and other applications |
US7181287B2 (en) * | 2001-02-13 | 2007-02-20 | Second Sight Medical Products, Inc. | Implantable drug delivery device |
US6875165B2 (en) * | 2001-02-22 | 2005-04-05 | Retinalabs, Inc. | Method of radiation delivery to the eye |
ATE506929T1 (en) | 2001-06-12 | 2011-05-15 | Univ Johns Hopkins Med | RESERVOIR DEVICE FOR INTRAOCULAR MEDICINAL DELIVERY |
DE60215373T2 (en) * | 2001-06-18 | 2007-08-23 | Durect Corp., Cupertino | DEVICE FOR DISTRIBUTING MICRO-DOSES OF A MEDICAMENT IN THE EAR |
AU2002319606B2 (en) * | 2001-07-23 | 2006-09-14 | Alcon, Inc. | Ophthalmic drug delivery device |
PT1409065E (en) * | 2001-07-23 | 2007-03-30 | Alcon Inc | Ophthalmic drug delivery device |
US7090888B2 (en) * | 2002-01-18 | 2006-08-15 | Snyder Michael E | Sustained release ophthalmological device and method of making and using the same |
US7108685B2 (en) * | 2002-04-15 | 2006-09-19 | Boston Scientific Scimed, Inc. | Patch stabilization of rods for treatment of cardiac muscle |
WO2003092665A2 (en) * | 2002-05-02 | 2003-11-13 | Massachusetts Eye And Ear Infirmary | Ocular drug delivery systems and use thereof |
ATE346544T1 (en) * | 2002-07-09 | 2006-12-15 | Anglo Europ College Of Chiropr | METHOD FOR IMAGING THE RELATIVE MOVEMENT OF SKELETON SEGMENTS |
US7008403B1 (en) * | 2002-07-19 | 2006-03-07 | Cognitive Ventures Corporation | Infusion pump and method for use |
US7699882B2 (en) * | 2002-09-17 | 2010-04-20 | Iscience Interventional Corporation | Apparatus and method for surgical bypass of aqueous humor |
CA2498489C (en) * | 2002-09-29 | 2010-02-23 | Surmodics, Inc. | Method for subretinal administration of therapeutics including steroids;method for localizing pharmacodynamic action at the choroid and the retina; and related methods for treatment and/or prevention of retinal diseases |
US7008411B1 (en) * | 2002-09-30 | 2006-03-07 | Advanced Cardiovascular Systems, Inc. | Method and apparatus for treating vulnerable plaque |
US20060265043A1 (en) * | 2002-09-30 | 2006-11-23 | Evgenia Mandrusov | Method and apparatus for treating vulnerable plaque |
US7326238B1 (en) | 2002-09-30 | 2008-02-05 | Abbott Cardiovascular Systems Inc. | Method and apparatus for treating vulnerable plaque |
WO2004073551A2 (en) * | 2003-02-18 | 2004-09-02 | Massachusetts Eye And Ear Infirmary | Transscleral drug delivery device and related methods |
ATE476960T1 (en) * | 2003-05-02 | 2010-08-15 | Surmodics Inc | SYSTEM FOR THE CONTROLLED RELEASE OF A BIOACTIVE INGREDIENT IN THE BACK OF THE EYE |
US8246974B2 (en) | 2003-05-02 | 2012-08-21 | Surmodics, Inc. | Medical devices and methods for producing the same |
US20040225250A1 (en) | 2003-05-05 | 2004-11-11 | Michael Yablonski | Internal shunt and method for treating glaucoma |
US20040265356A1 (en) * | 2003-06-30 | 2004-12-30 | Bausch & Lomb Incorporated | Drug delivery device |
JP2007526019A (en) * | 2003-07-10 | 2007-09-13 | アルコン,インコーポレイティド | Ophthalmic drug delivery device |
EP3168304A1 (en) * | 2003-08-27 | 2017-05-17 | Ophthotech Corporation | Combination therapy for the treatment of ocular neovascular disorders |
CN102144961A (en) * | 2003-09-18 | 2011-08-10 | 参天制药株式会社 | Transscleral delivery |
US20050181018A1 (en) * | 2003-09-19 | 2005-08-18 | Peyman Gholam A. | Ocular drug delivery |
US7291125B2 (en) * | 2003-11-14 | 2007-11-06 | Transcend Medical, Inc. | Ocular pressure regulation |
EP1689333B1 (en) * | 2003-12-05 | 2014-02-12 | Innfocus, Inc. | Improved glaucoma implant device |
US20050148948A1 (en) * | 2003-12-19 | 2005-07-07 | Caputa Steven G. | Sutureless ophthalmic drug delivery system and method |
US7976520B2 (en) * | 2004-01-12 | 2011-07-12 | Nulens Ltd. | Eye wall anchored fixtures |
IL159818A0 (en) * | 2004-01-12 | 2004-06-20 | Nulens Ltd | Intraocular structure |
US20050222613A1 (en) * | 2004-02-05 | 2005-10-06 | Edwin Ryan | Wound closure device and method for vitrectomy |
US7563222B2 (en) * | 2004-02-12 | 2009-07-21 | Neovista, Inc. | Methods and apparatus for intraocular brachytherapy |
AU2005214040B2 (en) * | 2004-02-12 | 2011-03-31 | Neo Vista, Inc. | Methods and apparatus for intraocular brachytherapy |
US20060083772A1 (en) * | 2004-04-06 | 2006-04-20 | Dewitt David M | Coating compositions for bioactive agents |
CN1964748A (en) * | 2004-04-06 | 2007-05-16 | 苏莫迪克斯公司 | Coating compositions for bioactive agents |
US20100173866A1 (en) * | 2004-04-29 | 2010-07-08 | Iscience Interventional Corporation | Apparatus and method for ocular treatment |
KR20070036044A (en) * | 2004-04-29 | 2007-04-02 | 아이싸이언스 인터벤셔날 코포레이션 | Apparatus and method for ocular treatment |
MXPA06012460A (en) * | 2004-04-29 | 2007-07-13 | Iscience Surgical Corp | Apparatus and method for surgical enhancement of aqueous humor drainage. |
US20050244471A1 (en) * | 2004-04-30 | 2005-11-03 | Allergan, Inc. | Estradiol derivative and estratopone containing sustained release intraocular implants and related methods |
US8119154B2 (en) * | 2004-04-30 | 2012-02-21 | Allergan, Inc. | Sustained release intraocular implants and related methods |
US20050267520A1 (en) | 2004-05-12 | 2005-12-01 | Modesitt D B | Access and closure device and method |
US20060024350A1 (en) * | 2004-06-24 | 2006-02-02 | Varner Signe E | Biodegradable ocular devices, methods and systems |
DK1765454T3 (en) * | 2004-07-02 | 2016-05-02 | Mati Therapeutics Inc | Device for submission of treatment medium to eye |
US7678133B2 (en) | 2004-07-10 | 2010-03-16 | Arstasis, Inc. | Biological tissue closure device and method |
US7117870B2 (en) * | 2004-07-26 | 2006-10-10 | Clarity Corporation | Lacrimal insert having reservoir with controlled release of medication and method of manufacturing the same |
US9138228B2 (en) | 2004-08-11 | 2015-09-22 | Emory University | Vascular conduit device and system for implanting |
WO2006023130A2 (en) * | 2004-08-12 | 2006-03-02 | Surmodics, Inc. | Biodegradable controlled release bioactive agent delivery device |
US8246569B1 (en) | 2004-08-17 | 2012-08-21 | California Institute Of Technology | Implantable intraocular pressure drain |
US20060110429A1 (en) * | 2004-11-24 | 2006-05-25 | Therakine Corporation | Implant for intraocular drug delivery |
WO2006068898A1 (en) * | 2004-12-22 | 2006-06-29 | Bausch & Lomb Incorporated | Reusable drug delivery device |
US20060147491A1 (en) * | 2005-01-05 | 2006-07-06 | Dewitt David M | Biodegradable coating compositions including multiple layers |
US20060198868A1 (en) * | 2005-01-05 | 2006-09-07 | Dewitt David M | Biodegradable coating compositions comprising blends |
WO2006083946A2 (en) * | 2005-02-01 | 2006-08-10 | Osteobiologics, Inc. | Method and device for selective addition of a bioactive agent to a multi-phase implant |
US8663639B2 (en) * | 2005-02-09 | 2014-03-04 | Santen Pharmaceutical Co., Ltd. | Formulations for treating ocular diseases and conditions |
WO2006086750A1 (en) * | 2005-02-09 | 2006-08-17 | Macusight, Inc. | Liquid formulations for treatment of diseases or conditions |
US20060233858A1 (en) * | 2005-03-08 | 2006-10-19 | Allergan, Inc. | Systems and methods providing targeted intraocular drug delivery |
US20070077270A1 (en) * | 2005-03-28 | 2007-04-05 | Clemson University | Delivery devices and methods for long-term, targeted delivery of therapeutic agents to the eye and ear |
US20060259008A1 (en) * | 2005-04-27 | 2006-11-16 | Allergan, Inc. | Apparatus and methods useful for intravitreal injection of drugs |
CN101217916B (en) | 2005-05-12 | 2013-04-10 | 阿尔斯塔西斯公司 | Access and closure device and method |
US20060258994A1 (en) * | 2005-05-12 | 2006-11-16 | Avery Robert L | Implantable delivery device for administering pharmacological agents to an internal portion of a body |
US20080207499A1 (en) * | 2005-06-29 | 2008-08-28 | Gaetano Barile | Rage-related methods for treating and preventing diabetic retinopathy |
US8109913B2 (en) * | 2005-07-11 | 2012-02-07 | Dsm Ip Assets B.V. | Coiled wire for the controlled release of drugs to the eye |
US20070060887A1 (en) * | 2005-08-22 | 2007-03-15 | Marsh David A | Ophthalmic injector |
US20070212397A1 (en) * | 2005-09-15 | 2007-09-13 | Roth Daniel B | Pharmaceutical delivery device and method for providing ocular treatment |
EP1926504B1 (en) * | 2005-09-21 | 2010-01-13 | SurModics, Inc. | In situ occluding compositions ncluding natural biodegradable polysaccharides |
US20080167600A1 (en) * | 2005-09-26 | 2008-07-10 | Peyman Gholam A | Device for delivery of an agent to the eye and other sites |
NZ568694A (en) | 2005-11-09 | 2011-09-30 | Zalicus Inc | Method, compositions, and kits for the treatment of medical conditions |
CA2629648A1 (en) * | 2005-11-15 | 2007-05-24 | Neovista Inc. | Methods and apparatus for intraocular brachytherapy |
JP5180834B2 (en) | 2005-11-29 | 2013-04-10 | スミスクライン ビーチャム コーポレーション | Method of treatment |
CA2636716C (en) * | 2006-01-13 | 2014-12-23 | Surmodics, Inc. | Microparticle containing matrices for drug delivery |
EP3632385A1 (en) | 2006-01-17 | 2020-04-08 | Novartis AG | Glaucoma treatment device |
WO2007084582A2 (en) | 2006-01-17 | 2007-07-26 | Forsight Labs, Llc | Drug delivery treatment device |
JP4881959B2 (en) * | 2006-01-17 | 2012-02-22 | ニューレンズ・リミテッド | Intraocular drug dispenser |
GB0600903D0 (en) * | 2006-01-17 | 2006-02-22 | Cancer Rec Tech Ltd | Treatment of cancer |
JP5528708B2 (en) | 2006-02-09 | 2014-06-25 | 参天製薬株式会社 | Stable formulations and methods for preparing and using them |
JP5681362B2 (en) * | 2006-03-14 | 2015-03-04 | ユニバーシティー オブ サザン カリフォルニア | MEMS device for delivery of therapeutic agents |
US8222271B2 (en) | 2006-03-23 | 2012-07-17 | Santen Pharmaceutical Co., Ltd. | Formulations and methods for vascular permeability-related diseases or conditions |
US8676293B2 (en) * | 2006-04-13 | 2014-03-18 | Aecc Enterprises Ltd. | Devices, systems and methods for measuring and evaluating the motion and function of joint structures and associated muscles, determining suitability for orthopedic intervention, and evaluating efficacy of orthopedic intervention |
US7981096B2 (en) * | 2006-05-12 | 2011-07-19 | David Castillejos | Optic nerve head implant and medication delivery system |
US7862540B2 (en) * | 2006-05-17 | 2011-01-04 | Alcon Research, Ltd. | Ophthalmic injection device using shape memory alloy |
US7887521B2 (en) * | 2006-05-17 | 2011-02-15 | Alcon Research, Ltd. | Ophthalmic injection system |
US7674243B2 (en) * | 2006-05-17 | 2010-03-09 | Alcon Inc. | Ophthalmic injection device using piezoelectric array |
US20070270750A1 (en) * | 2006-05-17 | 2007-11-22 | Alcon, Inc. | Drug delivery device |
US7811252B2 (en) * | 2006-05-17 | 2010-10-12 | Alcon Research, Ltd. | Dosage control device |
US20070270744A1 (en) * | 2006-05-17 | 2007-11-22 | Bruno Dacquay | Limited Reuse Assembly For Ophthalmic Injection Device |
US20070268340A1 (en) * | 2006-05-17 | 2007-11-22 | Bruno Dacquay | Ophthalmic Injection System and Method Using Piezoelectric Array |
US8668676B2 (en) * | 2006-06-19 | 2014-03-11 | Allergan, Inc. | Apparatus and methods for implanting particulate ocular implants |
US20070293873A1 (en) * | 2006-06-19 | 2007-12-20 | Allergan, Inc. | Apparatus and methods for implanting particulate ocular implants |
US7638344B2 (en) * | 2006-06-28 | 2009-12-29 | Surmodics, Inc. | Active agent eluting matrices with particulates |
US8911496B2 (en) | 2006-07-11 | 2014-12-16 | Refocus Group, Inc. | Scleral prosthesis for treating presbyopia and other eye disorders and related devices and methods |
US9039761B2 (en) | 2006-08-04 | 2015-05-26 | Allergan, Inc. | Ocular implant delivery assemblies with distal caps |
US20080057106A1 (en) * | 2006-08-29 | 2008-03-06 | Erickson Signe R | Low profile bioactive agent delivery device |
US20080097379A1 (en) * | 2006-09-26 | 2008-04-24 | Alcon Manufacturing, Ltd. | Ophthalmic injection method |
US20080125712A1 (en) * | 2006-09-26 | 2008-05-29 | Alcon Manufacturing, Ltd. | Ophthalmic injection system |
US20080097390A1 (en) * | 2006-09-27 | 2008-04-24 | Alcon Manufacturing, Ltd. | Spring actuated delivery system |
EP2068828A2 (en) * | 2006-09-29 | 2009-06-17 | SurModics, Inc. | Biodegradable ocular implants and methods for treating ocular conditions |
CN102014987A (en) * | 2006-10-16 | 2011-04-13 | 爱尔康研究有限公司 | Method of operating ophthalmic hand piece with disposable end |
US20080281292A1 (en) * | 2006-10-16 | 2008-11-13 | Hickingbotham Dyson W | Retractable Injection Port |
US9022970B2 (en) * | 2006-10-16 | 2015-05-05 | Alcon Research, Ltd. | Ophthalmic injection device including dosage control device |
EP2063829B1 (en) * | 2006-10-16 | 2010-12-08 | Alcon Research, Ltd. | Universal rechargeable limited reuse assembly for ophthalmic hand piece |
US20090005869A1 (en) * | 2006-12-15 | 2009-01-01 | University Of Virginia Patent Foundation | Device which Attaches into a Joint and Carries a Payload of Controlled Release Drugs and Related Method thereof |
US20080147021A1 (en) * | 2006-12-15 | 2008-06-19 | Jani Dharmendra M | Drug delivery devices |
CN103622778A (en) * | 2006-12-18 | 2014-03-12 | 爱尔康研究有限公司 | Devices and methods for ophthalmic drug delivery |
US7846123B2 (en) | 2007-04-24 | 2010-12-07 | Emory University | Conduit device and system for implanting a conduit device in a tissue wall |
US20080265343A1 (en) * | 2007-04-26 | 2008-10-30 | International Business Machines Corporation | Field effect transistor with inverted t shaped gate electrode and methods for fabrication thereof |
US9125807B2 (en) * | 2007-07-09 | 2015-09-08 | Incept Llc | Adhesive hydrogels for ophthalmic drug delivery |
EP2173289A4 (en) | 2007-07-17 | 2010-11-24 | Transcend Medical Inc | Ocular implant with hydrogel expansion capabilities |
US7740619B2 (en) | 2007-08-01 | 2010-06-22 | Alcon Research, Ltd. | Spring driven ophthalmic injection device with safety actuator lockout feature |
US20090036842A1 (en) * | 2007-08-03 | 2009-02-05 | Raffi Pinedjian | Consumable Activation Lever For Injection Device |
US20090099481A1 (en) * | 2007-10-10 | 2009-04-16 | Adam Deitz | Devices, Systems and Methods for Measuring and Evaluating the Motion and Function of Joints and Associated Muscles |
US20090105744A1 (en) * | 2007-10-17 | 2009-04-23 | Modesitt D Bruce | Methods for forming tracts in tissue |
EP2214608B1 (en) | 2007-11-08 | 2015-03-04 | Alimera Sciences, Inc. | Ocular implantation device |
MX364408B (en) | 2007-12-20 | 2019-04-25 | Univ Southern California | APPARATUS and METHODS FOR DELIVERING THERAPEUTIC AGENTS. |
JP2011509120A (en) | 2008-01-03 | 2011-03-24 | ユニバーシティ オブ サザン カリフォルニア | Implantable drug delivery device and apparatus and method for refilling the device |
JP2011510750A (en) | 2008-01-29 | 2011-04-07 | クライマン、ギルバート・エイチ | Drug delivery device, kit and methods thereof |
US20100152646A1 (en) * | 2008-02-29 | 2010-06-17 | Reshma Girijavallabhan | Intravitreal injection device and method |
US20090227938A1 (en) * | 2008-03-05 | 2009-09-10 | Insitu Therapeutics, Inc. | Wound Closure Devices, Methods of Use, and Kits |
US20140276681A1 (en) | 2013-03-15 | 2014-09-18 | Optimedica Corporation | Microfemtotomy methods and systems |
WO2009128944A2 (en) * | 2008-04-18 | 2009-10-22 | Surmodics, Inc. | Coating systems for the controlled delivery of hydrophilic bioactive agents |
WO2009137785A2 (en) * | 2008-05-08 | 2009-11-12 | Replenish Pumps, Llc | Drug-delivery pumps and methods of manufacture |
WO2009137780A2 (en) * | 2008-05-08 | 2009-11-12 | Replenish Pumps, Llc | Implantable pumps and cannulas therefor |
CN104758999B (en) | 2008-05-08 | 2018-08-07 | 迷你泵有限责任公司 | Implantable drug delivery devices and the device and method for filling the device |
US9849238B2 (en) | 2008-05-08 | 2017-12-26 | Minipumps, Llc | Drug-delivery pump with intelligent control |
EP2296756A1 (en) | 2008-06-04 | 2011-03-23 | Neovista, Inc. | Handheld radiation delivery system for advancing a radiation source wire |
ES2640867T3 (en) | 2008-06-25 | 2017-11-07 | Novartis Ag | Eye implant with ability to change shape |
JP2011528606A (en) * | 2008-07-21 | 2011-11-24 | アルスタシス,インコーポレイテッド | Apparatus and method for forming a tract in tissue |
JP2011528605A (en) * | 2008-07-21 | 2011-11-24 | アルスタシス,インコーポレイテッド | Device, method, and kit for forming a tube in tissue |
US8459310B2 (en) * | 2008-07-24 | 2013-06-11 | Surmodics, Inc. | Systems and methods for filling medical device lumen |
EP2367527A2 (en) | 2008-11-26 | 2011-09-28 | SurModics, Inc. | Implantable ocular drug delivery device and methods |
EP2376019A1 (en) * | 2008-12-19 | 2011-10-19 | QLT, Inc. | Substance delivering punctum implants and methods |
TW201026300A (en) * | 2009-01-02 | 2010-07-16 | Alcon Res Ltd | In-situ refillable ophthalmic implant |
US8545554B2 (en) * | 2009-01-16 | 2013-10-01 | Allergan, Inc. | Intraocular injector |
US8425473B2 (en) | 2009-01-23 | 2013-04-23 | Iscience Interventional Corporation | Subretinal access device |
US20100191177A1 (en) * | 2009-01-23 | 2010-07-29 | Iscience Interventional Corporation | Device for aspirating fluids |
JP5524983B2 (en) | 2009-01-28 | 2014-06-18 | トランセンド・メディカル・インコーポレイテッド | Implant system |
CA2757037C (en) | 2009-01-29 | 2019-08-06 | Forsight Vision4, Inc. | Posterior segment drug delivery |
US8623395B2 (en) | 2010-01-29 | 2014-01-07 | Forsight Vision4, Inc. | Implantable therapeutic device |
US20100191168A1 (en) | 2009-01-29 | 2010-07-29 | Trustees Of Tufts College | Endovascular cerebrospinal fluid shunt |
US8409606B2 (en) | 2009-02-12 | 2013-04-02 | Incept, Llc | Drug delivery through hydrogel plugs |
WO2010107826A2 (en) * | 2009-03-16 | 2010-09-23 | Endoshape, Inc. | Reliably retained shape memory ophthal-mological implants |
US8632511B2 (en) | 2009-05-06 | 2014-01-21 | Alcon Research, Ltd. | Multiple thermal sensors in a multiple processor environment for temperature control in a drug delivery device |
WO2010132835A1 (en) * | 2009-05-15 | 2010-11-18 | Arstasis, Inc. | Devices, methods and kits for forming tracts in tissue |
WO2010141553A1 (en) | 2009-06-02 | 2010-12-09 | Surmodics, Inc. | SILANE-FUNCTIONALIZED HYDROPHOBIC a(1→4)GLUCOPYRANOSE POLYMERS AND POLYMERIC MATRICES FOR IMPLANTATION OR INJECTION |
JP5695035B2 (en) | 2009-06-03 | 2015-04-01 | フォーサイト・ビジョン5・インコーポレイテッドForsight Vision5,Inc. | Anterior eye drug supply |
WO2011014704A2 (en) | 2009-07-30 | 2011-02-03 | Tandem Diabetes Care, Inc. | Infusion pump system with disposable cartridge having pressure venting and pressure feedback |
EP2467797B1 (en) * | 2009-08-18 | 2017-07-19 | MiniPumps, LLC | Electrolytic drug-delivery pump with adaptive control |
US20110054445A1 (en) * | 2009-09-02 | 2011-03-03 | Board Of Regents, The University Of Texas System | Devices and Methods for Treatment of Eye Disease |
US8545431B2 (en) * | 2009-09-21 | 2013-10-01 | Alcon Research, Ltd. | Lumen clearing valve for glaucoma drainage device |
US8721580B2 (en) * | 2009-09-21 | 2014-05-13 | Alcon Research, Ltd. | Power saving glaucoma drainage device |
US8419673B2 (en) | 2009-09-21 | 2013-04-16 | Alcon Research, Ltd. | Glaucoma drainage device with pump |
US8257295B2 (en) | 2009-09-21 | 2012-09-04 | Alcon Research, Ltd. | Intraocular pressure sensor with external pressure compensation |
AU2010298315A1 (en) * | 2009-09-22 | 2012-04-19 | Arstasis, Inc. | Devices, methods, and kits for forming tracts in tissue |
WO2011038236A2 (en) | 2009-09-25 | 2011-03-31 | Ortho Kinematics, Inc. | Systems and devices for an integrated imaging system with real-time feedback loops and methods therefor |
WO2011039648A1 (en) | 2009-09-30 | 2011-04-07 | Glaxo Wellcome Manufacturing Pte Ltd. | Methods of administration and treatment |
EP2482863A1 (en) | 2009-09-30 | 2012-08-08 | SurModics, Inc. | Hydrophobic polysaccharides with silyl ether linkages having enhanced degradation and medical articles made therefrom |
US20110105990A1 (en) * | 2009-11-04 | 2011-05-05 | Silvestrini Thomas A | Zonal drug delivery device and method |
US8177747B2 (en) | 2009-12-22 | 2012-05-15 | Alcon Research, Ltd. | Method and apparatus for drug delivery |
US8529492B2 (en) | 2009-12-23 | 2013-09-10 | Trascend Medical, Inc. | Drug delivery devices and methods |
US20110159098A1 (en) * | 2009-12-30 | 2011-06-30 | Surmodics, Inc. | Stabilization and delivery of nucleic acid complexes |
US20110184310A1 (en) * | 2010-01-27 | 2011-07-28 | Joe Denton Brown | Method of heating a shape memory alloy of a surgical instrument |
US10166142B2 (en) | 2010-01-29 | 2019-01-01 | Forsight Vision4, Inc. | Small molecule delivery with implantable therapeutic device |
EP3195858B1 (en) | 2010-04-03 | 2019-08-07 | Praful Doshi | Medical devices including medicaments and methods of making and using same |
US10413506B2 (en) | 2010-04-03 | 2019-09-17 | Praful Doshi | Medical devices including medicaments and methods of making and using same including enhancing comfort, enhancing drug penetration, and treatment of myopia |
SI2563813T1 (en) | 2010-04-30 | 2015-12-31 | Alexion Pharmaceuticals, Inc. | Anti-c5a antibodies and methods for using the antibodies |
AU2011285548B2 (en) * | 2010-08-05 | 2014-02-06 | Forsight Vision4, Inc. | Combined drug delivery methods and apparatus |
RS61601B1 (en) | 2010-08-05 | 2021-04-29 | Forsight Vision4 Inc | Injector apparatus for drug delivery |
RS62540B1 (en) | 2010-08-05 | 2021-12-31 | Forsight Vision4 Inc | Apparatus to treat an eye |
US8961501B2 (en) | 2010-09-17 | 2015-02-24 | Incept, Llc | Method for applying flowable hydrogels to a cornea |
WO2012065006A2 (en) | 2010-11-11 | 2012-05-18 | Forsight Vision4, Inc. | Methods and apparatus to determine porous structures for drug delivery |
AU2011329656B2 (en) | 2010-11-19 | 2017-01-05 | Forsight Vision4, Inc. | Therapeutic agent formulations for implanted devices |
EP2667792B1 (en) | 2011-01-28 | 2020-05-06 | Apica Cardiovascular Limited | Systems for sealing a tissue wall puncture |
CA2826413A1 (en) | 2011-02-01 | 2012-08-09 | Georgia Tech Research Corporation | Systems for implanting and using a conduit within a tissue wall |
US9919099B2 (en) | 2011-03-14 | 2018-03-20 | Minipumps, Llc | Implantable drug pumps and refill devices therefor |
US10286146B2 (en) | 2011-03-14 | 2019-05-14 | Minipumps, Llc | Implantable drug pumps and refill devices therefor |
US9603997B2 (en) | 2011-03-14 | 2017-03-28 | Minipumps, Llc | Implantable drug pumps and refill devices therefor |
US8992503B2 (en) | 2011-03-27 | 2015-03-31 | Microsert Ltd. | Miniature implanted drug delivery devices and inserter systems for introducing such devices |
EP2726016B1 (en) | 2011-06-28 | 2023-07-19 | ForSight Vision4, Inc. | An apparatus for collecting a sample of fluid from a reservoir chamber of a therapeutic device for the eye |
EP2747679B1 (en) * | 2011-08-23 | 2016-12-21 | Simcha Milo | Device for creating temporary access and then closure |
WO2013040426A2 (en) * | 2011-09-14 | 2013-03-21 | Forsight Labs, Llc | Ocular insert apparatus and methods |
EP2755546A4 (en) * | 2011-09-15 | 2015-08-12 | Yoseph Yaacobi | Systems and methods for treating ear disorders |
WO2013040247A2 (en) | 2011-09-16 | 2013-03-21 | Forsight Vision4, Inc. | Fluid exchange apparatus and methods |
US10226417B2 (en) | 2011-09-16 | 2019-03-12 | Peter Jarrett | Drug delivery systems and applications |
US8585631B2 (en) | 2011-10-18 | 2013-11-19 | Alcon Research, Ltd. | Active bimodal valve system for real-time IOP control |
US8840578B2 (en) | 2011-12-09 | 2014-09-23 | Alcon Research, Ltd. | Multilayer membrane actuators |
US8579848B2 (en) | 2011-12-09 | 2013-11-12 | Alcon Research, Ltd. | Active drainage systems with pressure-driven valves and electronically-driven pump |
WO2013090197A1 (en) | 2011-12-12 | 2013-06-20 | Alcon Research, Ltd. | Active drainage systems with dual-input pressure-driven valves |
WO2013090231A1 (en) | 2011-12-13 | 2013-06-20 | Alcon Research, Ltd. | Active drainage systems with dual-input pressure-driven valves |
US9339187B2 (en) | 2011-12-15 | 2016-05-17 | Alcon Research, Ltd. | External pressure measurement system and method for an intraocular implant |
US9241829B2 (en) | 2011-12-20 | 2016-01-26 | Abbott Medical Optics Inc. | Implantable intraocular drug delivery apparatus, system and method |
WO2013116061A1 (en) | 2012-02-03 | 2013-08-08 | Forsight Vision4, Inc. | Insertion and removal methods and apparatus for therapeutic devices |
US10085633B2 (en) | 2012-04-19 | 2018-10-02 | Novartis Ag | Direct visualization system for glaucoma treatment |
US9241832B2 (en) | 2012-04-24 | 2016-01-26 | Transcend Medical, Inc. | Delivery system for ocular implant |
US9180242B2 (en) | 2012-05-17 | 2015-11-10 | Tandem Diabetes Care, Inc. | Methods and devices for multiple fluid transfer |
US20130317438A1 (en) | 2012-05-25 | 2013-11-28 | Arstasis, Inc. | Vascular access configuration |
US20130317481A1 (en) | 2012-05-25 | 2013-11-28 | Arstasis, Inc. | Vascular access configuration |
US10010513B2 (en) | 2012-05-25 | 2018-07-03 | Novartis Ag | Aqueous pharmaceutical composition containing a biologic therapeutic agent and guanidine or a guanidine derivative and an injection including the composition |
RU2650203C2 (en) | 2012-09-17 | 2018-04-11 | Новартис Аг | Expanding ocular implant devices |
WO2014066775A1 (en) | 2012-10-26 | 2014-05-01 | Forsight Vision5, Inc. | Ophthalmic system for sustained release of drug to eye |
US9763829B2 (en) | 2012-11-14 | 2017-09-19 | Novartis Ag | Flow promoting ocular implant |
US9572712B2 (en) | 2012-12-17 | 2017-02-21 | Novartis Ag | Osmotically actuated fluidic valve |
US9528633B2 (en) | 2012-12-17 | 2016-12-27 | Novartis Ag | MEMS check valve |
US9295389B2 (en) | 2012-12-17 | 2016-03-29 | Novartis Ag | Systems and methods for priming an intraocular pressure sensor in an intraocular implant |
WO2014117087A1 (en) | 2013-01-25 | 2014-07-31 | Apica Cardiovascular Limited | Systems and methods for percutaneous access, stabilization and closure of organs |
CA2905496A1 (en) | 2013-03-14 | 2014-09-25 | Forsight Vision4, Inc. | Systems for sustained intraocular delivery of low solubility compounds from a port delivery system implant |
US9173998B2 (en) | 2013-03-14 | 2015-11-03 | Tandem Diabetes Care, Inc. | System and method for detecting occlusions in an infusion pump |
EP2968717A4 (en) | 2013-03-15 | 2017-02-22 | Apk Advanced Medical Technologies, Inc. | Devices, systems, and methods for implanting and using a connnector in a tissue wall |
AU2014241163B2 (en) | 2013-03-28 | 2018-09-27 | Forsight Vision4, Inc. | Ophthalmic implant for delivering therapeutic substances |
US9987163B2 (en) | 2013-04-16 | 2018-06-05 | Novartis Ag | Device for dispensing intraocular substances |
MX2016000364A (en) | 2013-07-12 | 2016-05-09 | Ophthotech Corp | Methods for treating or preventing ophthalmological conditions. |
US9226851B2 (en) | 2013-08-24 | 2016-01-05 | Novartis Ag | MEMS check valve chip and methods |
US9283115B2 (en) | 2013-08-26 | 2016-03-15 | Novartis Ag | Passive to active staged drainage device |
US9289324B2 (en) | 2013-08-26 | 2016-03-22 | Novartis Ag | Externally adjustable passive drainage device |
EP3041524A4 (en) | 2013-09-06 | 2017-06-14 | The Regents of the University of Colorado, a body corporate | Intraocular drug delivery and filter device and methods of using same |
US11219552B2 (en) | 2013-09-06 | 2022-01-11 | The Regents Of The University Of Colorado, A Body Corporate | Intraocular filter device and methods of using same |
EP3998100A1 (en) | 2014-01-15 | 2022-05-18 | Tufts Medical Center, Inc. | Endovascular cerebrospinal fluid shunt system |
US9737696B2 (en) | 2014-01-15 | 2017-08-22 | Tufts Medical Center, Inc. | Endovascular cerebrospinal fluid shunt |
NZ631007A (en) | 2014-03-07 | 2015-10-30 | Alexion Pharma Inc | Anti-c5 antibodies having improved pharmacokinetics |
US9603742B2 (en) | 2014-03-13 | 2017-03-28 | Novartis Ag | Remote magnetic driven flow system |
US9681983B2 (en) | 2014-03-13 | 2017-06-20 | Novartis Ag | Debris clearance system for an ocular implant |
USD760381S1 (en) | 2014-06-25 | 2016-06-28 | Donald Fox | Orbital injection cannula |
WO2016011191A1 (en) | 2014-07-15 | 2016-01-21 | Forsight Vision4, Inc. | Ocular implant delivery device and method |
SG11201700943TA (en) | 2014-08-08 | 2017-03-30 | Forsight Vision4 Inc | Stable and soluble formulations of receptor tyrosine kinase inhibitors, and methods of preparation thereof |
CN107148293B (en) | 2014-10-31 | 2020-08-11 | 西瑞维斯克有限责任公司 | Methods and systems for treating hydrocephalus |
EP3212250A4 (en) | 2014-10-31 | 2018-07-11 | Thoratec Corporation | Apical connectors and instruments for use in a heart wall |
CA2967330A1 (en) | 2014-11-10 | 2016-05-19 | Forsight Vision4, Inc. | Expandable drug delivery devices and methods of use |
US9655777B2 (en) | 2015-04-07 | 2017-05-23 | Novartis Ag | System and method for diagphragm pumping using heating element |
US20160296532A1 (en) | 2015-04-13 | 2016-10-13 | Forsight Vision5, Inc. | Ocular Insert Composition of a Semi-Crystalline or Crystalline Pharmaceutically Active Agent |
US20160354161A1 (en) | 2015-06-05 | 2016-12-08 | Ortho Kinematics, Inc. | Methods for data processing for intra-operative navigation systems |
US10182939B2 (en) | 2015-09-16 | 2019-01-22 | Novartis Ag | Hydraulic injector and methods for intra-ocular lens insertion |
JP6820612B2 (en) | 2015-10-30 | 2021-01-27 | セレバスク,インコーポレイテッド | Hydrocephalus treatment system and method |
CN113069681B (en) | 2015-11-20 | 2022-12-23 | 弗赛特影像4股份有限公司 | Method of manufacturing a therapeutic device for sustained drug delivery |
CN108601725B (en) | 2015-11-25 | 2024-03-08 | 因赛普特有限责任公司 | Shape-changing drug delivery device and method |
ES2837524T3 (en) | 2016-04-05 | 2021-06-30 | Forsight Vision4 Inc | Implantable ocular drug delivery devices |
AU2018300237A1 (en) | 2017-07-14 | 2020-01-16 | Cytomx Therapeutics, Inc. | Anti-CD166 antibodies and uses thereof |
WO2019023564A1 (en) | 2017-07-27 | 2019-01-31 | Alexion Pharmaceutical, Inc. | High concentration anti-c5 antibody formulations |
CN107519532B (en) * | 2017-08-25 | 2020-10-02 | 唐山市工人医院 | Elastic prosthesis material and preparation method thereof |
CN111655206B (en) | 2017-11-21 | 2022-10-14 | 弗赛特影像4股份有限公司 | Fluid exchange device for expandable port delivery system and method of use |
EP3501433A1 (en) * | 2017-12-21 | 2019-06-26 | Universiteit Maastricht | Apparatus for handling a rod shaped element to be inserted into or removed from the eye of a patient |
US11013900B2 (en) | 2018-03-08 | 2021-05-25 | CereVasc, Inc. | Systems and methods for minimally invasive drug delivery to a subarachnoid space |
US11690806B2 (en) | 2018-05-24 | 2023-07-04 | Celanese Eva Performance Polymers Llc | Implantable device for sustained release of a macromolecular drug compound |
BR112020023983A2 (en) | 2018-05-24 | 2021-02-23 | Celanese Eva Performance Polymers Llc | implantable device for prolonged release of a macromolecular drug compound |
US20200100941A1 (en) * | 2018-08-25 | 2020-04-02 | Thad Anthony Labbe | Ophthalmic surgical instruments for removal of lens materials and methods of use |
BR112021012172A2 (en) | 2018-12-12 | 2021-08-31 | Kite Pharma, Inc. | CHIMERIC AND T-CELL ANTIGEN RECEPTORS AND METHODS OF USE |
CA3176425A1 (en) | 2020-04-24 | 2021-10-28 | Millennium Pharmaceuticals, Inc. | Anti-cd19 antibodies and uses thereof |
JP2024515066A (en) | 2021-04-09 | 2024-04-04 | 武田薬品工業株式会社 | Antibodies targeting complement factor D and uses thereof |
EP4330283A1 (en) | 2021-04-26 | 2024-03-06 | Millennium Pharmaceuticals, Inc. | Anti-adgre2 antibodies and uses thereof |
AR125451A1 (en) | 2021-04-26 | 2023-07-19 | Millennium Pharm Inc | ANTI-CLEC12A ANTIBODIES AND USES THEREOF |
WO2023068382A2 (en) | 2021-10-20 | 2023-04-27 | Takeda Pharmaceutical Company Limited | Compositions targeting bcma and methods of use thereof |
Citations (34)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4014334A (en) * | 1976-02-02 | 1977-03-29 | Alza Corporation | Laminated osmotic system for dispensing beneficial agent |
US4206756A (en) * | 1977-03-23 | 1980-06-10 | Murray Grossan | Jet ear irrigation system |
US4300557A (en) * | 1980-01-07 | 1981-11-17 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Method for treating intraocular malignancies |
US4451254A (en) * | 1982-03-15 | 1984-05-29 | Eli Lilly And Company | Implant system |
US4678466A (en) * | 1981-06-25 | 1987-07-07 | Rosenwald Peter L | Internal medication delivery method and vehicle |
US4701180A (en) * | 1986-02-19 | 1987-10-20 | Kelly L Thomas | Implanted anchor and insert with analog display |
US4853224A (en) * | 1987-12-22 | 1989-08-01 | Visionex | Biodegradable ocular implants |
US5098443A (en) * | 1989-03-23 | 1992-03-24 | University Of Miami | Method of implanting intraocular and intraorbital implantable devices for the controlled release of pharmacological agents |
US5164188A (en) * | 1989-11-22 | 1992-11-17 | Visionex, Inc. | Biodegradable ocular implants |
US5300114A (en) * | 1992-05-04 | 1994-04-05 | Allergan, Inc. | Subconjunctival implants for ocular drug delivery |
US5364343A (en) * | 1991-03-06 | 1994-11-15 | D.D. S.R.L. | Irrigation device for use in ear canals for therapeutic or hygienic purposes |
US5372577A (en) * | 1988-04-11 | 1994-12-13 | Ungerleider; Bruce A. | Apparatus for reducing intraocular pressure |
US5378475A (en) * | 1991-02-21 | 1995-01-03 | University Of Kentucky Research Foundation | Sustained release drug delivery devices |
US5395618A (en) * | 1986-10-02 | 1995-03-07 | Escalon Ophthalmics, Inc. | Ocular insert with anchoring protrusions |
US5443505A (en) * | 1993-11-15 | 1995-08-22 | Oculex Pharmaceuticals, Inc. | Biocompatible ocular implants |
US5466233A (en) * | 1994-04-25 | 1995-11-14 | Escalon Ophthalmics, Inc. | Tack for intraocular drug delivery and method for inserting and removing same |
US5472436A (en) * | 1994-07-26 | 1995-12-05 | Fremstad; Daria A. | Ocular appliance for delivering medication |
US5551427A (en) * | 1995-02-13 | 1996-09-03 | Altman; Peter A. | Implantable device for the effective elimination of cardiac arrhythmogenic sites |
US5582616A (en) * | 1994-08-05 | 1996-12-10 | Origin Medsystems, Inc. | Surgical helical fastener with applicator |
US5868697A (en) * | 1995-05-14 | 1999-02-09 | Optonol Ltd. | Intraocular implant |
US5904144A (en) * | 1996-03-22 | 1999-05-18 | Cytotherapeutics, Inc. | Method for treating ophthalmic diseases |
US5928662A (en) * | 1996-07-31 | 1999-07-27 | Phillips; Andrew F. | Ocular drug delivery device |
US5972369A (en) * | 1997-03-31 | 1999-10-26 | Alza Corporation | Diffusional implantable delivery system |
US5972027A (en) * | 1997-09-30 | 1999-10-26 | Scimed Life Systems, Inc | Porous stent drug delivery system |
US6074661A (en) * | 1997-08-11 | 2000-06-13 | Allergan Sales, Inc. | Sterile bioerodible occular implant device with a retinoid for improved biocompatability |
US6251090B1 (en) * | 1994-12-12 | 2001-06-26 | Robert Logan Avery | Intravitreal medicine delivery |
US6306125B1 (en) * | 1998-06-22 | 2001-10-23 | Neovasys, Inc. | Angiogenic implant delivery system and method |
US6397849B1 (en) * | 1998-08-03 | 2002-06-04 | Insite Vision Incorporated | Methods of ophthalmic administration |
US6478776B1 (en) * | 2000-04-05 | 2002-11-12 | Biocardia, Inc. | Implant delivery catheter system and methods for its use |
US20030120200A1 (en) * | 2000-04-14 | 2003-06-26 | Bergheim Olav B. | Apparatus and method for treating glaucoma |
US6706023B1 (en) * | 1999-12-03 | 2004-03-16 | Bionix Development Corporation | Device for irrigation of a blind orifice |
US6719750B2 (en) * | 2000-08-30 | 2004-04-13 | The Johns Hopkins University | Devices for intraocular drug delivery |
US6764470B2 (en) * | 2001-12-03 | 2004-07-20 | Roland P. Dimick | Ear plug medication administration device |
US20050240147A1 (en) * | 2004-04-21 | 2005-10-27 | Exploramed Ii, Inc. | Devices, systems and methods for diagnosing and treating sinusitus and other disorders of the ears, nose and/or throat |
Family Cites Families (56)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US273410A (en) * | 1883-03-06 | Gelatine eye-disk | ||
US3416530A (en) * | 1966-03-02 | 1968-12-17 | Richard A. Ness | Eyeball medication dispensing tablet |
US4069307A (en) * | 1970-10-01 | 1978-01-17 | Alza Corporation | Drug-delivery device comprising certain polymeric materials for controlled release of drug |
US4144317A (en) * | 1975-05-30 | 1979-03-13 | Alza Corporation | Device consisting of copolymer having acetoxy groups for delivering drugs |
US4304765A (en) * | 1980-10-14 | 1981-12-08 | Alza Corporation | Ocular insert housing steroid in two different therapeutic forms |
CA1232814A (en) | 1983-09-16 | 1988-02-16 | Hidetoshi Sakamoto | Guide wire for catheter |
US4892736A (en) * | 1983-10-07 | 1990-01-09 | The Forsyth Dental Infirmary For Children | Intra-pocket drug delivery devices for treatment of periodontal diseases |
US4764377A (en) * | 1983-10-07 | 1988-08-16 | The Forsyth Dental Infirmary For Children | Intra-pocket drug delivery devices for treatment of periodontal diseases |
US4665905A (en) | 1986-06-09 | 1987-05-19 | Brown Charles S | Dynamic elbow and knee extension brace |
US5989579A (en) * | 1986-10-02 | 1999-11-23 | Escalon Medical Corp. | Ocular insert with anchoring protrusions |
EP0390860B1 (en) | 1987-12-17 | 1995-04-12 | United States Surgical Corporation | Medical devices fabricated from homopolymers and copolymers having recurring carbonate units |
KR0185215B1 (en) * | 1990-11-30 | 1999-05-01 | 요시다 쇼오지 | A controlled-release pharmaceutical preparation for intra-ocular implant |
US5246867A (en) * | 1992-01-17 | 1993-09-21 | University Of Maryland At Baltimore | Determination and quantification of saccharides by luminescence lifetimes and energy transfer |
US5578075B1 (en) * | 1992-11-04 | 2000-02-08 | Daynke Res Inc | Minimally invasive bioactivated endoprosthesis for vessel repair |
US5464650A (en) * | 1993-04-26 | 1995-11-07 | Medtronic, Inc. | Intravascular stent and method |
CN100998869A (en) | 1993-07-19 | 2007-07-18 | 血管技术药物公司 | Anti-angiogene compositions and methods of use |
US5994341A (en) * | 1993-07-19 | 1999-11-30 | Angiogenesis Technologies, Inc. | Anti-angiogenic Compositions and methods for the treatment of arthritis |
US5605696A (en) | 1995-03-30 | 1997-02-25 | Advanced Cardiovascular Systems, Inc. | Drug loaded polymeric material and method of manufacture |
US6120536A (en) | 1995-04-19 | 2000-09-19 | Schneider (Usa) Inc. | Medical devices with long term non-thrombogenic coatings |
US5837313A (en) | 1995-04-19 | 1998-11-17 | Schneider (Usa) Inc | Drug release stent coating process |
US6099562A (en) | 1996-06-13 | 2000-08-08 | Schneider (Usa) Inc. | Drug coating with topcoat |
US5773019A (en) * | 1995-09-27 | 1998-06-30 | The University Of Kentucky Research Foundation | Implantable controlled release device to deliver drugs directly to an internal portion of the body |
ZA97976B (en) | 1996-04-05 | 1997-08-18 | Alza Corp | Uniform drug delivery theraphy. |
ZA978537B (en) * | 1996-09-23 | 1998-05-12 | Focal Inc | Polymerizable biodegradable polymers including carbonate or dioxanone linkages. |
US5997517A (en) | 1997-01-27 | 1999-12-07 | Sts Biopolymers, Inc. | Bonding layers for medical device surface coatings |
US5879697A (en) | 1997-04-30 | 1999-03-09 | Schneider Usa Inc | Drug-releasing coatings for medical devices |
US6110483A (en) | 1997-06-23 | 2000-08-29 | Sts Biopolymers, Inc. | Adherent, flexible hydrogel and medicated coatings |
BR9815499A (en) | 1997-07-02 | 2001-01-02 | Euro Celtique Sa | Prolonged anesthesia in joints and body spaces. |
US6306166B1 (en) | 1997-08-13 | 2001-10-23 | Scimed Life Systems, Inc. | Loading and release of water-insoluble drugs |
KR100289471B1 (en) | 1998-01-19 | 2001-09-17 | 김충섭 | A controlled/sustained implant delivery containing fentanyls |
US20020188037A1 (en) * | 1999-04-15 | 2002-12-12 | Chudzik Stephen J. | Method and system for providing bioactive agent release coating |
WO1999055396A1 (en) * | 1998-04-27 | 1999-11-04 | Surmodics, Inc. | Bioactive agent release coating |
US6013099A (en) * | 1998-04-29 | 2000-01-11 | Medtronic, Inc. | Medical device for delivering a water-insoluble therapeutic salt or substance |
US6153252A (en) * | 1998-06-30 | 2000-11-28 | Ethicon, Inc. | Process for coating stents |
NZ509797A (en) | 1998-07-10 | 2003-11-28 | Univ Sydney | Prophylactic treatments of neovascularisation in macular degeneration using a steroid |
US6399655B1 (en) * | 1998-12-22 | 2002-06-04 | Johns Hopkins University, School Of Medicine | Method for the prophylactic treatment of cataracts |
US20040121014A1 (en) * | 1999-03-22 | 2004-06-24 | Control Delivery Systems, Inc. | Method for treating and/or preventing retinal diseases with sustained release corticosteroids |
US6217895B1 (en) * | 1999-03-22 | 2001-04-17 | Control Delivery Systems | Method for treating and/or preventing retinal diseases with sustained release corticosteroids |
US6309660B1 (en) | 1999-07-28 | 2001-10-30 | Edwards Lifesciences Corp. | Universal biocompatible coating platform for medical devices |
US6331313B1 (en) | 1999-10-22 | 2001-12-18 | Oculex Pharmaceticals, Inc. | Controlled-release biocompatible ocular drug delivery implant devices and methods |
US6264971B1 (en) | 1999-11-04 | 2001-07-24 | Btg International Limited | Ocular insert |
US6245100B1 (en) | 2000-02-01 | 2001-06-12 | Cordis Corporation | Method for making a self-expanding stent-graft |
US7077848B1 (en) | 2000-03-11 | 2006-07-18 | John Hopkins University | Sutureless occular surgical methods and instruments for use in such methods |
US20020035176A1 (en) * | 2000-03-13 | 2002-03-21 | King Bruce A. | Flame retardant, high impact monovinylidene aromatic polymer composition |
US6375972B1 (en) * | 2000-04-26 | 2002-04-23 | Control Delivery Systems, Inc. | Sustained release drug delivery devices, methods of use, and methods of manufacturing thereof |
US6451373B1 (en) * | 2000-08-04 | 2002-09-17 | Advanced Cardiovascular Systems, Inc. | Method of forming a therapeutic coating onto a surface of an implantable prosthesis |
JP4583756B2 (en) | 2000-10-31 | 2010-11-17 | クック インコーポレイテッド | Medical instruments |
US6471980B2 (en) * | 2000-12-22 | 2002-10-29 | Avantec Vascular Corporation | Intravascular delivery of mycophenolic acid |
JP2004523275A (en) | 2000-12-22 | 2004-08-05 | アバンテク バスキュラー コーポレーション | Delivery of therapeutic drugs |
US6713081B2 (en) * | 2001-03-15 | 2004-03-30 | The United States Of America As Represented By The Department Of Health And Human Services | Ocular therapeutic agent delivery devices and methods for making and using such devices |
US20040022853A1 (en) * | 2001-04-26 | 2004-02-05 | Control Delivery Systems, Inc. | Polymer-based, sustained release drug delivery system |
ATE506929T1 (en) * | 2001-06-12 | 2011-05-15 | Univ Johns Hopkins Med | RESERVOIR DEVICE FOR INTRAOCULAR MEDICINAL DELIVERY |
US7485113B2 (en) * | 2001-06-22 | 2009-02-03 | Johns Hopkins University | Method for drug delivery through the vitreous humor |
US20030158598A1 (en) * | 2001-09-17 | 2003-08-21 | Control Delivery Systems, Inc. | System for sustained-release delivery of anti-inflammatory agents from a coated medical device |
DE60331552D1 (en) * | 2002-08-13 | 2010-04-15 | Medtronic Inc | PHARMACEUTICALS COMPOSITIONS USING POLY (ETHYLENE-CO (METH) ACRYLATE, MEDICAL DEVICE AND METHOD |
CA2498489C (en) | 2002-09-29 | 2010-02-23 | Surmodics, Inc. | Method for subretinal administration of therapeutics including steroids;method for localizing pharmacodynamic action at the choroid and the retina; and related methods for treatment and/or prevention of retinal diseases |
-
2001
- 2001-06-22 DE DE60135352T patent/DE60135352D1/en not_active Expired - Lifetime
- 2001-06-22 AU AU7141701A patent/AU7141701A/en active Pending
- 2001-06-22 EP EP01950424A patent/EP1313415B1/en not_active Expired - Lifetime
- 2001-06-22 PT PT01950424T patent/PT1313415E/en unknown
- 2001-06-22 JP JP2002522807A patent/JP4471568B2/en not_active Expired - Lifetime
- 2001-06-22 DK DK01950424T patent/DK1313415T3/en active
- 2001-06-22 AT AT01950424T patent/ATE404140T1/en not_active IP Right Cessation
- 2001-06-22 CA CA2420038A patent/CA2420038C/en not_active Expired - Fee Related
- 2001-06-22 AU AU2001271417A patent/AU2001271417B2/en not_active Ceased
- 2001-06-22 EP EP08014292A patent/EP1992317B1/en not_active Expired - Lifetime
- 2001-06-22 US US09/888,092 patent/US6719750B2/en not_active Expired - Lifetime
- 2001-06-22 WO PCT/US2001/020119 patent/WO2002017831A2/en active Application Filing
- 2001-06-22 ES ES01950424T patent/ES2312456T3/en not_active Expired - Lifetime
- 2001-06-22 AT AT08014292T patent/ATE547080T1/en active
-
2003
- 2003-12-19 US US10/740,698 patent/US8096972B2/en not_active Expired - Fee Related
-
2004
- 2004-04-12 US US10/823,089 patent/US20050059956A1/en not_active Abandoned
-
2007
- 2007-01-05 AU AU2007200057A patent/AU2007200057B2/en not_active Ceased
Patent Citations (38)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4014334A (en) * | 1976-02-02 | 1977-03-29 | Alza Corporation | Laminated osmotic system for dispensing beneficial agent |
US4206756A (en) * | 1977-03-23 | 1980-06-10 | Murray Grossan | Jet ear irrigation system |
US4300557A (en) * | 1980-01-07 | 1981-11-17 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Method for treating intraocular malignancies |
US4678466A (en) * | 1981-06-25 | 1987-07-07 | Rosenwald Peter L | Internal medication delivery method and vehicle |
US4451254A (en) * | 1982-03-15 | 1984-05-29 | Eli Lilly And Company | Implant system |
US4701180A (en) * | 1986-02-19 | 1987-10-20 | Kelly L Thomas | Implanted anchor and insert with analog display |
US5395618A (en) * | 1986-10-02 | 1995-03-07 | Escalon Ophthalmics, Inc. | Ocular insert with anchoring protrusions |
US4853224A (en) * | 1987-12-22 | 1989-08-01 | Visionex | Biodegradable ocular implants |
US5372577A (en) * | 1988-04-11 | 1994-12-13 | Ungerleider; Bruce A. | Apparatus for reducing intraocular pressure |
US5098443A (en) * | 1989-03-23 | 1992-03-24 | University Of Miami | Method of implanting intraocular and intraorbital implantable devices for the controlled release of pharmacological agents |
US5164188A (en) * | 1989-11-22 | 1992-11-17 | Visionex, Inc. | Biodegradable ocular implants |
US5378475A (en) * | 1991-02-21 | 1995-01-03 | University Of Kentucky Research Foundation | Sustained release drug delivery devices |
US5364343A (en) * | 1991-03-06 | 1994-11-15 | D.D. S.R.L. | Irrigation device for use in ear canals for therapeutic or hygienic purposes |
US5300114A (en) * | 1992-05-04 | 1994-04-05 | Allergan, Inc. | Subconjunctival implants for ocular drug delivery |
US5476511A (en) * | 1992-05-04 | 1995-12-19 | Allergan, Inc. | Subconjunctival implants for ocular drug delivery |
US5443505A (en) * | 1993-11-15 | 1995-08-22 | Oculex Pharmaceuticals, Inc. | Biocompatible ocular implants |
US5824072A (en) * | 1993-11-15 | 1998-10-20 | Oculex Pharmaceuticals, Inc. | Biocompatible ocular implants |
US5466233A (en) * | 1994-04-25 | 1995-11-14 | Escalon Ophthalmics, Inc. | Tack for intraocular drug delivery and method for inserting and removing same |
US5472436A (en) * | 1994-07-26 | 1995-12-05 | Fremstad; Daria A. | Ocular appliance for delivering medication |
US20020013605A1 (en) * | 1994-08-05 | 2002-01-31 | Lee Bolduc | Surgical helical fastener with applicator |
US5582616A (en) * | 1994-08-05 | 1996-12-10 | Origin Medsystems, Inc. | Surgical helical fastener with applicator |
US6251090B1 (en) * | 1994-12-12 | 2001-06-26 | Robert Logan Avery | Intravitreal medicine delivery |
US5551427A (en) * | 1995-02-13 | 1996-09-03 | Altman; Peter A. | Implantable device for the effective elimination of cardiac arrhythmogenic sites |
US5868697A (en) * | 1995-05-14 | 1999-02-09 | Optonol Ltd. | Intraocular implant |
US5904144A (en) * | 1996-03-22 | 1999-05-18 | Cytotherapeutics, Inc. | Method for treating ophthalmic diseases |
US5928662A (en) * | 1996-07-31 | 1999-07-27 | Phillips; Andrew F. | Ocular drug delivery device |
US5972369A (en) * | 1997-03-31 | 1999-10-26 | Alza Corporation | Diffusional implantable delivery system |
US6074661A (en) * | 1997-08-11 | 2000-06-13 | Allergan Sales, Inc. | Sterile bioerodible occular implant device with a retinoid for improved biocompatability |
US5972027A (en) * | 1997-09-30 | 1999-10-26 | Scimed Life Systems, Inc | Porous stent drug delivery system |
US6306125B1 (en) * | 1998-06-22 | 2001-10-23 | Neovasys, Inc. | Angiogenic implant delivery system and method |
US6397849B1 (en) * | 1998-08-03 | 2002-06-04 | Insite Vision Incorporated | Methods of ophthalmic administration |
US6706023B1 (en) * | 1999-12-03 | 2004-03-16 | Bionix Development Corporation | Device for irrigation of a blind orifice |
US6478776B1 (en) * | 2000-04-05 | 2002-11-12 | Biocardia, Inc. | Implant delivery catheter system and methods for its use |
US20030120200A1 (en) * | 2000-04-14 | 2003-06-26 | Bergheim Olav B. | Apparatus and method for treating glaucoma |
US6719750B2 (en) * | 2000-08-30 | 2004-04-13 | The Johns Hopkins University | Devices for intraocular drug delivery |
US20040133155A1 (en) * | 2000-08-30 | 2004-07-08 | Varner Sign Erickson | Devices for intraocular drug delivery |
US6764470B2 (en) * | 2001-12-03 | 2004-07-20 | Roland P. Dimick | Ear plug medication administration device |
US20050240147A1 (en) * | 2004-04-21 | 2005-10-27 | Exploramed Ii, Inc. | Devices, systems and methods for diagnosing and treating sinusitus and other disorders of the ears, nose and/or throat |
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US20070027452A1 (en) * | 2005-05-18 | 2007-02-01 | Varner Signe E | Insertion instrument for non-linear medical devices |
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US8166909B2 (en) | 2005-11-15 | 2012-05-01 | Surmodics, Inc. | Apparatus and methods for applying coatings |
US20070128343A1 (en) * | 2005-11-15 | 2007-06-07 | Chappa Ralph A | Apparatus And Methods for Applying Coatings |
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US20110008526A1 (en) * | 2006-09-25 | 2011-01-13 | Surmodics, Inc. | Multi-layered coatings and methods for controlling elution of active agents |
US8142836B2 (en) | 2006-09-25 | 2012-03-27 | Surmodics, Inc. | Multi-layered coatings and methods for controlling elution of active agents |
US20080075779A1 (en) * | 2006-09-27 | 2008-03-27 | Chappa Ralph A | Additives And Methods For Enhancing Active Agent Elution Kinetics |
US7831309B1 (en) | 2006-12-06 | 2010-11-09 | University Of Southern California | Implants based on bipolar metal oxide semiconductor (MOS) electronics |
US20100004581A1 (en) * | 2008-01-07 | 2010-01-07 | Salutarismd | Methods and devices for minimally-invasive extraocular delivery of radiation to the posterior portion of the eye |
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US20090263449A1 (en) * | 2008-04-09 | 2009-10-22 | Surmodics, Inc. | Delivery of nucleic acid complexes from materials including negatively charged groups |
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Also Published As
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DE60135352D1 (en) | 2008-09-25 |
EP1313415B1 (en) | 2008-08-13 |
EP1992317A2 (en) | 2008-11-19 |
JP4471568B2 (en) | 2010-06-02 |
ES2312456T3 (en) | 2009-03-01 |
US6719750B2 (en) | 2004-04-13 |
EP1992317B1 (en) | 2012-02-29 |
AU2007200057A1 (en) | 2007-01-25 |
WO2002017831A3 (en) | 2002-07-11 |
US20020026176A1 (en) | 2002-02-28 |
JP2004524866A (en) | 2004-08-19 |
US20040133155A1 (en) | 2004-07-08 |
ATE404140T1 (en) | 2008-08-15 |
PT1313415E (en) | 2008-11-25 |
AU7141701A (en) | 2002-03-13 |
DK1313415T3 (en) | 2008-10-13 |
WO2002017831A2 (en) | 2002-03-07 |
EP1313415A2 (en) | 2003-05-28 |
AU2001271417B2 (en) | 2006-10-05 |
US8096972B2 (en) | 2012-01-17 |
CA2420038A1 (en) | 2002-03-07 |
AU2007200057B2 (en) | 2008-09-18 |
ATE547080T1 (en) | 2012-03-15 |
CA2420038C (en) | 2010-11-09 |
EP1992317A3 (en) | 2009-01-21 |
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