US3618604A - Ocular insert - Google Patents

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US3618604A
US3618604A US831761A US3618604DA US3618604A US 3618604 A US3618604 A US 3618604A US 831761 A US831761 A US 831761A US 3618604D A US3618604D A US 3618604DA US 3618604 A US3618604 A US 3618604A
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drug
medication
polymeric material
dispensing tablet
tablet
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Richard A Ness
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Alza Corp
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Alza Corp
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F9/00Methods 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
    • A61F9/0008Introducing ophthalmic products into the ocular cavity or retaining products therein
    • A61F9/0017Introducing ophthalmic products into the ocular cavity or retaining products therein implantable in, or in contact with, the eye, e.g. ocular inserts
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0048Eye, e.g. artificial tears
    • A61K9/0051Ocular inserts, ocular implants

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  • Drug-dispensing ocular insert is comprised of a flexible body of polymeric material that is insoluble in tear liquid and has an imperforate surface.
  • the polymeric material contains a drug which is dispensed to the eye in a therapeuti cally effective amount by diffusion through the polymeric material.
  • the ocular insert is adapted for insertion in the culde-sac of the conjunctiva between the sclera of the eyeball and the lower lid, to be held in place against the eyeball by the pressure of the lid.
  • PATENTEUNUV 91971 3.618504 mvsmron RICHARD A. NESS BACKGROUND OF THE INVENTION This invention relates to an ocular insert for dispensing drugs to the eye over a prolonged period of time.
  • U.S. Pat. No. 3,416,530 granted Dec. 17, 1968, and assigned to the assignee of this invention, is directed to my invention of a drug-dispensing ocular insert that truly acts as a depot or drug reservoir, retaining and slowly releasing drug to the eye for prolonged periods of time.
  • ocular inserts are fabricated of flexible polymeric materials that are biologically inert, nonallergenic, and insoluble in tear liquid.
  • the ocular insert is placed in the culde-sac of the conjunctiva between the sclera of the eyeball and the lid.
  • the polymeric material from which the ocular insert is formed is insoluble in tear liquid it retains its integrity and remains intact during the course of therapy, acting as a reservoir to continuously release drug to the eye and sur rounding tissues at a rate which is not affected by dissolution or erosion of the polymeric material.
  • the ocular insert is removed from the cul-de-sac.
  • a single such ocular insert provides the complete ophthalmic dosage regime for a particular time period, on the order of 24 hours or longer. Frequent repeated applications, as is necessary with liquids, ointments, or watersoluble lamellae, often requiring awakening the patient during the night, are avoided.
  • U.S. Pat. No. 3,416,530 describes using polymeric materials which are perforated with capillary openings. While these capillary openings are effective to release drug to the eye, they add considerable complexity to the manufacture of ocular inserts; for its is difficult to control the size of these openings in large-scale manufacturing using various polymers.
  • Still another object of this invention dependent upon the size and pores in the polymeric body of the is to provide a drugdispensing ocular insert which is comfortable to wear for long resides in a drug-dispensing ocular insert periods and does not cause discomfort during sleeping and normal daily wear.
  • one feature of this invention to deliver during to the eye over aprolonged period of time comprising a flexible ody of polymeric material insoluble in tear liquid and having an imperforate surface, the body containing a drugwhichis dispensed to the eye in a therapeutically effective amount by diffusion through the polymeric material.
  • the ocular insert of this invention is adapted for insertion in the cul-de-sac of the conjunctiva betweenthe sclera of the eyeball and the lower lid, to be held in place against the eyeball by the pressure of the lid.
  • insert is designed for placement and eyelid and is fabricated of a perforate surface, that therethrough.
  • Polymeric materials used in forming the ocular insert are flexible, biologically inert, insoluble in tear liquid, and nonallergenic. It is important that thepolyrneric material be capable of transferring the drug through its unbrokenwalls by the diffusion of drug or drug solution therethrough. By utilizing the mechanism of difiusion to dispense drug to the eye, the rate of drug release can be controlled with precision and reproducibility. In each case, selection of the polymeric material is dependent on the particular drug and drug form to be used in the device.
  • Exemplary materials forfabricating the ocular insert include hydrophobic polymers such as plasticized or unplasticized polyvinylchloride, plasticized nylon, unplasticized soft nylon, plasticized polyethylene terephtahalate, and silicone rubber; and hydrophilic polymers such as the hydrophilic hydrogels of esters of acrylic and methacrylic acid (as described in U.S. Pat. Nos. 2,976,576 and 3,220,960 and modified collagen, cross-linked hydrophilic polyether gels (as described in U.S. Pat. No. 3,419,006), cross-linked polyvinylalcohol, and cross-linked partially hydrolyzed polyvinylacetate.
  • various plasticizers kriown to the art can be employed, such as long-chain fatty amides, higher alcohols, and dioctyl phthalate.
  • hydrophilic polymers suitable for use in this invention absorb forming a hydrogel therewith. Tear liquid entering to form the swollen hydrogel molecules dissolves the drug within the polymeric body, and the resulting drug solution then diffuses outwardly from: the the hydrogel structure. Therefore, as used in this specification and the appended claims, the term diffusion? refers to the movement of a drug through an imperforate polymeric body, as well as to the movement of adrug solution through an imperforate body.
  • insoluble in tear liquidf means that the polymeric materials do not dissolve and erode as a result of the action of tear liquid, but may absorb tear liquid, forming a swollen hydrogel.
  • any of the drugs used to treat the eye and surrounding tissues can be incorporated in the ocular insert of this invention.
  • drugs which will pass through the eye or the tissue surrounding the eye to the bloodstream, but which are not used in therapy of the eye itself can be incorporated in the ocular insert.
  • Suitable drugs for use in therapy of the eye with the ocular insert include, without limitation: Anti-infectives: such as antibiotics, including tetracycline, chlortetracycleine, bacitracin, neomycin, polymyxin, gramicidin, oxytetracycline, chloramphenicol, and erythromycin; sulfonamides, including sulfacetamide, sulfamethizole, and sulfisoxazole; antivirals, including idoxuridine; and other anti-infectives including nitrofurazone and sodium propionate; Antiallergenics such as antazoline, methapyrilene, chlorpheniramine, pyrilamine and prophenpyridamine; Anti-inflammatories such as hydrocortisone, hydrocortisone acetate, dexamethasone, dexamethasone 2l-phosphate, fluocinolone, medrysone, prednisolone, pred
  • Drugs can be in various forms, such as uncharged molecules, components of molecular complexes, or nonirritating, pharmacologically acceptable salts, such as hydrochloride, hydrobromide, sulfate phosphate, nitrate, borate, acetate, maleate, tartrate, salicylate, etc.
  • pharmacologically acceptable salts such as hydrochloride, hydrobromide, sulfate phosphate, nitrate, borate, acetate, maleate, tartrate, salicylate, etc.
  • simple derivatives of the drugs such as ethers, esters, amides, etc., which have desirable retention and release characteristics but which are easily hydrolyzed by body pH, enzymes, etc. can be employed.
  • the amount of drug incorporated in the ocular insert varies widely, depending on the particular drug, the desired therapeutic effect, and the time span for which the ocular insert will be used.
  • the ocular insert is intended to provide the complete dosage regime for eye therapy for but a particular time span, such as 24 hours, there is no critical upper limit on the amount of drug incorporated in the device. For when the device is removed and disposed of it makes little difference whether any drug remains in the device. The lower limit will depend on the activity of the drug and its capability of being released from the device. Thus it is not practical to define a range for the therapeutically effective amount of drug incorporated into the device. However, typically, from I microgram to l milligram of drug is incorporated in the ocular insert.
  • the polymeric material used to form the ocular insert is chosen for its compatibility with a particular drug and its capability of releasing that drug by diffusion at an appropriate rate over a prolonged period of time.
  • Specific, but nonlimiting, examples of combinations of drugs and polymers for use in forming the ocular insert are: (l) chloramphenicol incorporated into polyethylene terephthalate plasticized with higher alcohols; (2) promethazine trichloroacetate incorporated into polyvinylchloride plasticized with dioctylphthalate; (3) chloramphenicol dispersed throughout polydimethylsiloxane rubber; (4) pilocarpine or pilocarpine perfluorobutyrate incorporated into polyvinylchloride plasticized with dioctylsebecate; and (5) dexamethasone incorporated into nylon-plasticized with higher alcohols.
  • the ocular insert can be fabricated in any convenient shape for comfortable retention in the cul-de-sac. It is important, however, that the device have no sharp, jagged, or rough edges which can irritate the sensitive tissues of the eye.
  • the marginal outline of the ocular insert can be ellipsoid, beanshaped, rectangular, etc. In cross section, in can be concavoconvex, rectangular, etc.
  • the ocular insert is flexible and, in used, will assume essentially the configuration of the scleral curvature, the original shape of the device is not of controlling importance. Dimensions of the device can vary widely.
  • the lower limit on the size of the device is governed by the amount of the particular drug to be applied to the eye and surrounding tissues to elicit the desired pharmacologic response, as well as by the smallest sized device which conveniently can be inserted and removed from the eye.
  • the upper limit on the size of the device is governed by the limited space within the culde-sac that conveniently and comfortably can be filled with an ocular insert.
  • the ocular insert is 4 to 20 millimeters in length, l to 12 millimeters in width, and 0.1 to l millimeter in thickness.
  • it is ellipsoidal in shape and about 6 X4 0.5 millimeters in size.
  • the ocular insert can be a polymeric matrix with the drug dispersed therethrough or can be a sealed container with walls of polymeric material and having the drug in an interior chamber thereof.
  • One such container has a circular or ellipsoidal cross section and is tapered at the ends.
  • Drug can be incorporated in the ocular insert in many ways. When the ocular insert is in the form of a container, any of the encapsulation, bonding, and coating techniques conventionally used in the art can be employed.
  • the ocular insert When the ocular insert is a solid matrix with the drug dispersed therethrough, it can be fabricated by adding the drugs to the monomers prior to polymerization; adding the drug to the polymer in liquid form, molding and curing; or by impregnating the polymeric material, either before or after shaping to the form of the ocular insert, with the drug.
  • the ocular insert 10 (shown by dot and dash lines in FIG. 1), it is placed in the cul-de-sac ll of the conjunctiva 12 between sclera 13 of the eyeball l4 and the lower lid 15.
  • the pressure of the lower lid 15 maintains the ocular insert 10 in place.
  • the ocular insert 10 With the ocular insert 10 under the lower lid 15, the device is comfortable to the wearer and does not contact the cornea 16 during sleeping nor during normal ocular motion.
  • the ocular insert 10 functions as a drug reservoir gradually releasing drug to the eye and surrounding tissue. Drug 17 leaving the ocular insert by diffusion is transported to the eyeball 14 by the flow of tear liquid and by the blinking action of the eyelids.
  • the eye is continuously bathed with drug 17 over a particular time span. Normally, the ocular insert 10 will be retained in place for a period of 24 hours, thereby supplying the complete dosage regime for eye therapy over that period of time.
  • the polymeric body 18 of the ocular insert does not dissolve or erode in tear liquid and a predictable and reproducible dosage regime is provided.
  • liquid polydimethylsiloxane (dow Corning Silastic 382) is mixed with chloramphenicol antibiotic.
  • stannous octoate catalyst 0.5 percent by weight is added to the mixture is poured into a mold having an ellipsoidal cavity 6 millimeters by 4 millimeters by 0.5 millimeter to cure the silicone rubber at room temperature.
  • the resulting ocular insert formed of silicone rubber contains 0.5 milligram of chloramphenicol.
  • the ocular insert When inserted in the cul-de-sac of the conjunctiva between the sclera of the eyeball and the lower lid, the ocular insert is effective to deliver to the eye the dose of chloramphenicol antibiotic required for 24 hours of treatment of infection. After that period of time, the ocular insert, with its dimensions unchanged, is removed from the cul-desac and an identical insert placed in its stead to continue the therapeutic program for an additional 24 -hour period.
  • the improved ocular insert of this invention offers many advantages. As it is formed of a polymeric material, insoluble in tear liquid, the ocular insert does not dissolve or erode in tear liquid during the course of therapeutic program. This permits the therapeutic program to be precisely controlled and the release of drug predicted with accuracy. That the ocular insert releases drug by diffusion is most important, since this too provides for close control over the rate of drug release from the polymer.
  • a medication-dispensing tablet for a human eyeball comprising a reservoir of drug formulation confined within a flexible, imperforate and continuous-surfaced body of nonallergenic polymeric material which is insoluble in tear liquid, said body being formed of a drug-release rate-controlling polymer to continuously meter the flow of drug by diffusion from the reservoir to the eye at a controlled, predetermined and reproducible rate over a prolonged period of time, said body being adapted for insertion into the cul-de-sac of the conjunctiva between the sclera of the eyeball and eyelid, to be held in place against the eyeball by the pressure of the lid, and said body having a marginal outline and cross section adapted to assume essentially the configuration of the scleral curvature; said drug being capable of transport through the unbroken walls of said body by diffusion and said body being so constructed and arranged that, when applied to the eyeball, to dispense said drug leaving said body by diffusion is transported to the eyeball by the flow of tears and by
  • polymeric material is selected from the group consisting of plasticized or unplasticized polyvinyl chloride, plasticized nylon, unplasticized soft nylon, plasticized polyethylene terephthalate, silicone rubber, hydrophilic hydrogel of an ester of acrylic or methacrylic acid, modified collagen, cross-linked hydrophilic polyether gel, cross-linked polyvinyl alcohol, and cross-linked partially hydrolyzed polyvinyl acetate.
  • polymeric material is selected from the group consisting of plasticized unplasticized polyvinyl chloride, plasticized nylon, unplasticized soft nylon, plasticized polyethylene terephthalate, silicone rubber, hydrophilic hydrogel of an ester of acrylic or methacrylic acid, modified collagen, cross-linked hydrophilic polyether gel, cross-linked polyvinyl acetate.
  • the medication-dispensing tablet as defined by claim I wherein same ranges from 4 to 20 millimeters in length, l to 12 millimeters in width, and 0.1 to l millimeter in thickness.
  • Claim 7, line 2 insert or between “plasticized” and “unplasticized”. Claim 7, line 7, after "polyvinyl delete “acetate.” and insert alcohol, and cross-linked partially hydrolyzed polyvinyl acetate.--. Claim 20, line 47, "perfluorbutyrate” should read perfluorobutyrate.

Abstract

Drug-dispensing ocular insert is comprised of a flexible body of polymeric material that is insoluble in tear liquid and has an imperforate surface. The polymeric material contains a drug which is dispensed to the eye in a therapeutically effective amount by diffusion through the polymeric material. The ocular insert is adapted for insertion in the cul-de-sac of the conjunctiva between the sclera of the eyeball and the lower lid, to be held in place against the eyeball by the pressure of the lid.

Description

United States Patent Inventor Richard A. Ness Fergus Falls, Minn. App]. No. 831,761 Filed June 9, 1969 Patented Nov. 9, 1971 Assignee Alza Corporation OCULAR INSERT 21 Claims, 2 Drawing Figs. US. Cl. 128/260, 128/156 lnt .Cl ..A6lm 31/00 Field 01 Search 128/260, 296, 156
[56] References Cited UNITED STATES PATENTS 3,220,960 1 1/ 1965 Wichterle 260/25 3,339,546 9/1967, Chen 128/156 3,416,530 12/1968 Ness 128/260 Primary Examiner-Robert W. Michell Assistant ExaminerR. P. Dyer Attorney-Steven D. Goldby ABSTRACT: Drug-dispensing ocular insert is comprised of a flexible body of polymeric material that is insoluble in tear liquid and has an imperforate surface. The polymeric material contains a drug which is dispensed to the eye in a therapeuti cally effective amount by diffusion through the polymeric material. The ocular insert is adapted for insertion in the culde-sac of the conjunctiva between the sclera of the eyeball and the lower lid, to be held in place against the eyeball by the pressure of the lid.
PATENTEUNUV 91971 3.618504 mvsmron RICHARD A. NESS BACKGROUND OF THE INVENTION This invention relates to an ocular insert for dispensing drugs to the eye over a prolonged period of time.
At the present time, diseases of the eye are treated by applying ophtahalmic drugs in liquid or ointment form. To be effective in many cases, the application of drug should be substantially continuous. Such continuous delivery of drug is not obtained through the use of liquid or ointment dosage forms, even though they be applied at intervals during the day and night. Periodic application of these dosage forms results in the eye receiving a massive, but unpredictable, amount of drug at the time of application but the drug is washed away rapidly by tears, leaving the eye without medication until the nextapplication. Ointment dosage forms are presently available only in unsterilized form and this too presents a problem.
At a very early time, drugs were dissolved or'dispersed in a water-soluble gel of gylcerinated gelatin that was shaped to the form of a lamella or eye disk. These lamellae were applied to the inner surface of the eyelid to supply drug to the eye. In use, the glycerinated gelatin vehicle liquid, producing the fonns. Lamellae were same type of effect as liquid dosage not a sustained-release dosage form. To my knowledge, they are not used in this country, although they may be' used to a small extent in Europe. Further information on these water-soluble dosage forms can be found in Remingtons Pharmaceutical Sciences, Xlll, pages 547-8 (Mack Publishing Co., Easton, Pa. 1965); Fishbum, An Introduction to Pharmaceutical Formulation, page 116 (Pergamon Press Ltd, New York Cit NY. 1965); and U.S. Pat. No. 273,410,Mar.6, 1883.
U.S. Pat. No. 3,416,530, granted Dec. 17, 1968, and assigned to the assignee of this invention, is directed to my invention of a drug-dispensing ocular insert that truly acts as a depot or drug reservoir, retaining and slowly releasing drug to the eye for prolonged periods of time. Such ocular inserts are fabricated of flexible polymeric materials that are biologically inert, nonallergenic, and insoluble in tear liquid. To initiate the therapeutic program, the ocular insert is placed in the culde-sac of the conjunctiva between the sclera of the eyeball and the lid. Since the polymeric material from which the ocular insert is formed is insoluble in tear liquid it retains its integrity and remains intact during the course of therapy, acting as a reservoir to continuously release drug to the eye and sur rounding tissues at a rate which is not affected by dissolution or erosion of the polymeric material. On termination of the therapeutic program, the ocular insert is removed from the cul-de-sac. Thus, a single such ocular insert provides the complete ophthalmic dosage regime for a particular time period, on the order of 24 hours or longer. Frequent repeated applications, as is necessary with liquids, ointments, or watersoluble lamellae, often requiring awakening the patient during the night, are avoided.
To provide for release of ophthalmic drug from the polymeric body of the ocular insert, U.S. Pat. No. 3,416,530 describes using polymeric materials which are perforated with capillary openings. While these capillary openings are effective to release drug to the eye, they add considerable complexity to the manufacture of ocular inserts; for its is difficult to control the size of these openings in large-scale manufacturing using various polymers.
The best mode contemplated for practicing the invention of U.S. Pat. 3,416,530, was, at the time the patent application maturing to that patent was filed, to place the ocular insert under the upper eyelid in generally radically spaced relation to the cornea of the eyeball and in the path of flow of tears from the associated lachrymal gland. However, the eye has a tendency to roll upwardly during sleeping a process known as Bell's Phenomenon, which may cause discomfort to some persons if the ocular insert is under the upper lid.
dissolved'rapidly in tear 2 SUMMARY OF THE INVENTION dispensing ocular insert which delivers drugs to the eye at a controlled rate, that is not number of perforations or ocular insert. 7
Still another object of this invention dependent upon the size and pores in the polymeric body of the is to provide a drugdispensing ocular insert which is comfortable to wear for long resides in a drug-dispensing ocular insert periods and does not cause discomfort during sleeping and normal daily wear. In accomplishing these objects, one feature of this invention to deliver during to the eye over aprolonged period of time, comprising a flexible ody of polymeric material insoluble in tear liquid and having an imperforate surface, the body containing a drugwhichis dispensed to the eye in a therapeutically effective amount by diffusion through the polymeric material. The ocular insert of this invention is adapted for insertion in the cul-de-sac of the conjunctiva betweenthe sclera of the eyeball and the lower lid, to be held in place against the eyeball by the pressure of the lid.
Other objects features and advantages of the invention will become more apparent from the following description of the invention and from the claims.
.Belgian Pat. No. 701,813),
DETAILED DESCRlPTlON or THE INVENTION In accordance with this invention, insert is designed for placement and eyelid and is fabricated of a perforate surface, that therethrough.
Polymeric materials used in forming the ocular insert are flexible, biologically inert, insoluble in tear liquid, and nonallergenic. It is important that thepolyrneric material be capable of transferring the drug through its unbrokenwalls by the diffusion of drug or drug solution therethrough. By utilizing the mechanism of difiusion to dispense drug to the eye, the rate of drug release can be controlled with precision and reproducibility. In each case, selection of the polymeric material is dependent on the particular drug and drug form to be used in the device. Exemplary materials forfabricating the ocular insert include hydrophobic polymers such as plasticized or unplasticized polyvinylchloride, plasticized nylon, unplasticized soft nylon, plasticized polyethylene terephtahalate, and silicone rubber; and hydrophilic polymers such as the hydrophilic hydrogels of esters of acrylic and methacrylic acid (as described in U.S. Pat. Nos. 2,976,576 and 3,220,960 and modified collagen, cross-linked hydrophilic polyether gels (as described in U.S. Pat. No. 3,419,006), cross-linked polyvinylalcohol, and cross-linked partially hydrolyzed polyvinylacetate. When plasticizers are used to impart flexibility to the polymer, various plasticizers kriown to the art can be employed, such as long-chain fatty amides, higher alcohols, and dioctyl phthalate.
Those skilled in the art will appreciate that many of the hydrophilic polymers suitable for use in this invention absorb forming a hydrogel therewith. Tear liquid entering to form the swollen hydrogel molecules dissolves the drug within the polymeric body, and the resulting drug solution then diffuses outwardly from: the the hydrogel structure. Therefore, as used in this specification and the appended claims, the term diffusion? refers to the movement of a drug through an imperforate polymeric body, as well as to the movement of adrug solution through an imperforate body. Use of the expression insoluble in tear liquidf to refer to suitable polymeric materials, means that the polymeric materials do not dissolve and erode as a result of the action of tear liquid, but may absorb tear liquid, forming a swollen hydrogel.
a drug-dispensing ocular retention under the lower polymeric material, having an imwill release drug by diffusion Any of the drugs used to treat the eye and surrounding tissues can be incorporated in the ocular insert of this invention. Also, it is practical to use the eye and surrounding tissues as a point of entry for systemic drugs that enter circulation in the blood stream and produce a phannacologic response at a site remote from the point of application of the ocular insert. Thus, drugs which will pass through the eye or the tissue surrounding the eye to the bloodstream, but which are not used in therapy of the eye itself, can be incorporated in the ocular insert.
Suitable drugs for use in therapy of the eye with the ocular insert include, without limitation: Anti-infectives: such as antibiotics, including tetracycline, chlortetracycleine, bacitracin, neomycin, polymyxin, gramicidin, oxytetracycline, chloramphenicol, and erythromycin; sulfonamides, including sulfacetamide, sulfamethizole, and sulfisoxazole; antivirals, including idoxuridine; and other anti-infectives including nitrofurazone and sodium propionate; Antiallergenics such as antazoline, methapyrilene, chlorpheniramine, pyrilamine and prophenpyridamine; Anti-inflammatories such as hydrocortisone, hydrocortisone acetate, dexamethasone, dexamethasone 2l-phosphate, fluocinolone, medrysone, prednisolone, prednisolone ZI-phosphate and prednisolone acetate; Decongestants such as phenylephrine, naphazoline, and tetrahydrazoline; Miotics and anticholinesterases such as pilocarpine, eserine salicylate, carbachol, diisopropyl flur'ophosphate, phospholine iodide, and demecarium bromide; Mydriatics such as atropine sulfate, cyclopentolate, homatropine, scopolamine, tropicamide, eucatropine, and hydroxyamphetamine and Sypathomimetics such as epinephrine. Drugs can be in various forms, such as uncharged molecules, components of molecular complexes, or nonirritating, pharmacologically acceptable salts, such as hydrochloride, hydrobromide, sulfate phosphate, nitrate, borate, acetate, maleate, tartrate, salicylate, etc. Furthermore, simple derivatives of the drugs (such as ethers, esters, amides, etc.,) which have desirable retention and release characteristics but which are easily hydrolyzed by body pH, enzymes, etc. can be employed. The amount of drug incorporated in the ocular insert varies widely, depending on the particular drug, the desired therapeutic effect, and the time span for which the ocular insert will be used. Since the ocular insert is intended to provide the complete dosage regime for eye therapy for but a particular time span, such as 24 hours, there is no critical upper limit on the amount of drug incorporated in the device. For when the device is removed and disposed of it makes little difference whether any drug remains in the device. The lower limit will depend on the activity of the drug and its capability of being released from the device. Thus it is not practical to define a range for the therapeutically effective amount of drug incorporated into the device. However, typically, from I microgram to l milligram of drug is incorporated in the ocular insert.
In each case, the polymeric material used to form the ocular insert is chosen for its compatibility with a particular drug and its capability of releasing that drug by diffusion at an appropriate rate over a prolonged period of time. Specific, but nonlimiting, examples of combinations of drugs and polymers for use in forming the ocular insert are: (l) chloramphenicol incorporated into polyethylene terephthalate plasticized with higher alcohols; (2) promethazine trichloroacetate incorporated into polyvinylchloride plasticized with dioctylphthalate; (3) chloramphenicol dispersed throughout polydimethylsiloxane rubber; (4) pilocarpine or pilocarpine perfluorobutyrate incorporated into polyvinylchloride plasticized with dioctylsebecate; and (5) dexamethasone incorporated into nylon-plasticized with higher alcohols.
The ocular insert can be fabricated in any convenient shape for comfortable retention in the cul-de-sac. It is important, however, that the device have no sharp, jagged, or rough edges which can irritate the sensitive tissues of the eye. Thus the marginal outline of the ocular insert can be ellipsoid, beanshaped, rectangular, etc. In cross section, in can be concavoconvex, rectangular, etc. As the ocular insert is flexible and, in used, will assume essentially the configuration of the scleral curvature, the original shape of the device is not of controlling importance. Dimensions of the device can vary widely. The lower limit on the size of the device is governed by the amount of the particular drug to be applied to the eye and surrounding tissues to elicit the desired pharmacologic response, as well as by the smallest sized device which conveniently can be inserted and removed from the eye. The upper limit on the size of the device is governed by the limited space within the culde-sac that conveniently and comfortably can be filled with an ocular insert. Typically, the ocular insert is 4 to 20 millimeters in length, l to 12 millimeters in width, and 0.1 to l millimeter in thickness. Preferably it is ellipsoidal in shape and about 6 X4 0.5 millimeters in size.
The ocular insert can be a polymeric matrix with the drug dispersed therethrough or can be a sealed container with walls of polymeric material and having the drug in an interior chamber thereof. One such container has a circular or ellipsoidal cross section and is tapered at the ends. Drug can be incorporated in the ocular insert in many ways. When the ocular insert is in the form of a container, any of the encapsulation, bonding, and coating techniques conventionally used in the art can be employed. When the ocular insert is a solid matrix with the drug dispersed therethrough, it can be fabricated by adding the drugs to the monomers prior to polymerization; adding the drug to the polymer in liquid form, molding and curing; or by impregnating the polymeric material, either before or after shaping to the form of the ocular insert, with the drug.
Referring particularly to FIG. 1 and 2, to use the ocular insert 10 (shown by dot and dash lines in FIG. 1), it is placed in the cul-de-sac ll of the conjunctiva 12 between sclera 13 of the eyeball l4 and the lower lid 15. The pressure of the lower lid 15 maintains the ocular insert 10 in place. With the ocular insert 10 under the lower lid 15, the device is comfortable to the wearer and does not contact the cornea 16 during sleeping nor during normal ocular motion. Once in place, the ocular insert 10 functions as a drug reservoir gradually releasing drug to the eye and surrounding tissue. Drug 17 leaving the ocular insert by diffusion is transported to the eyeball 14 by the flow of tear liquid and by the blinking action of the eyelids. By use of the ocular insert, the eye is continuously bathed with drug 17 over a particular time span. Normally, the ocular insert 10 will be retained in place for a period of 24 hours, thereby supplying the complete dosage regime for eye therapy over that period of time. During the course of use, the polymeric body 18 of the ocular insert does not dissolve or erode in tear liquid and a predictable and reproducible dosage regime is provided.
In a specific example of the manufacture of an ocular insert the invention, liquid polydimethylsiloxane (dow Corning Silastic 382) is mixed with chloramphenicol antibiotic. After uniformly mixing the antibiotic with the unvulcanized silicone rubber, stannous octoate catalyst (0.5 percent by weight) is added to the mixture is poured into a mold having an ellipsoidal cavity 6 millimeters by 4 millimeters by 0.5 millimeter to cure the silicone rubber at room temperature. The resulting ocular insert formed of silicone rubber contains 0.5 milligram of chloramphenicol. When inserted in the cul-de-sac of the conjunctiva between the sclera of the eyeball and the lower lid, the ocular insert is effective to deliver to the eye the dose of chloramphenicol antibiotic required for 24 hours of treatment of infection. After that period of time, the ocular insert, with its dimensions unchanged, is removed from the cul-desac and an identical insert placed in its stead to continue the therapeutic program for an additional 24 -hour period.
Thus, the improved ocular insert of this invention offers many advantages. As it is formed of a polymeric material, insoluble in tear liquid, the ocular insert does not dissolve or erode in tear liquid during the course of therapeutic program. This permits the therapeutic program to be precisely controlled and the release of drug predicted with accuracy. That the ocular insert releases drug by diffusion is most important, since this too provides for close control over the rate of drug release from the polymer.
While there have been described and pointed out the fundamental novel features of the invention as applied to the preferred embodiment, those skilled in the art will appreciate that various modifications, changes, and omissions in the ocular insert illustrated and described can be made without departing from the spirit of the invention. It is the intention, therefore, to be limited only by the scope of the following claims.
What is claimed is:
l. A medication-dispensing tablet for a human eyeball, said tablet comprising a reservoir of drug formulation confined within a flexible, imperforate and continuous-surfaced body of nonallergenic polymeric material which is insoluble in tear liquid, said body being formed of a drug-release rate-controlling polymer to continuously meter the flow of drug by diffusion from the reservoir to the eye at a controlled, predetermined and reproducible rate over a prolonged period of time, said body being adapted for insertion into the cul-de-sac of the conjunctiva between the sclera of the eyeball and eyelid, to be held in place against the eyeball by the pressure of the lid, and said body having a marginal outline and cross section adapted to assume essentially the configuration of the scleral curvature; said drug being capable of transport through the unbroken walls of said body by diffusion and said body being so constructed and arranged that, when applied to the eyeball, to dispense said drug leaving said body by diffusion is transported to the eyeball by the flow of tears and by the blinking action of the eyelids.
2. The medication-dispensing tablet as defined by claim 1, wherein the reservoir of drug formulation is comprised of a sealed container with walls of said polymeric material and said drug is contained in an interior chamber thereof.
3. The medication-dispensing tablet as defined by claim 2, wherein said polymeric material is selected from the group consisting of plasticized or unplasticized polyvinyl chloride, plasticized nylon, unplasticized soft nylon, plasticized polyethylene terephthalate, silicone rubber, hydrophilic hydrogel of an ester of acrylic or methacrylic acid, modified collagen, cross-linked hydrophilic polyether gel, cross-linked polyvinyl alcohol, and cross-linked partially hydrolyzed polyvinyl acetate.
4. The medication-dispensing tablet as defined by claim 3, wherein said polymeric material is silicone rubber.
5. The medication-dispensing tablet as defined by claim 3, wherein said polymeric material is a hydrophilic hydrogel of an ester of acrylic or methacrylic acid.
6. The medication-dispensing tablet as defined by claim 1, wherein the reservoir of drug formulation is comprised of a matrix of the drug-release ratecontrolling polymeric material, said matrix having the drug distributed therethrough.
7. The medication-dispensing tablet as defined by claim 1,
wherein said polymeric material is selected from the group consisting of plasticized unplasticized polyvinyl chloride, plasticized nylon, unplasticized soft nylon, plasticized polyethylene terephthalate, silicone rubber, hydrophilic hydrogel of an ester of acrylic or methacrylic acid, modified collagen, cross-linked hydrophilic polyether gel, cross-linked polyvinyl acetate.
8. The medication-dispensing tablet as defined by claim 7, wherein said polymeric material is silicone rubber.
9. The medication-dispensing tablet as defined by claim 7, wherein said polymeric material is a hydrophilic hydrogel of an ester of acrylic or methacrylic acid.
10. The medication-dispensing tablet as defined by claim 1, wherein said drug is an ophthalmic drug.
11. The medication-dispensing tablet as defined by claim 1, wherein said drug is a systemically active drug which will pass through the eye to the bloodstream and produce a pharmacologic response at a site remote from the eye.
vl2. The medication-dispensing tablet as defined by claim 1, wherein said drug is a systemically active drug which will pass through the tissue surrounding the eye to the bloodstream and produce a pharmacologic response at a site remote from the l3. The medication-dispensing tablet as defined by claim 1, wherein from 1 microgram to l milligram of drug is incorporated in said tablet.
14. The medication-dispensing tablet as defined by claim 1,
I wherein same is circular in cross section and tapered at its ends.
15. The medication-dispensing tablet as defined by claim 1, wherein same is ellipsoidal in cross section and tapered at its ends.
16. The medication-dispensing tablet as defined by claim I, wherein same ranges from 4 to 20 millimeters in length, l to 12 millimeters in width, and 0.1 to l millimeter in thickness.
17. The medication-dispensing tablet as defined by claim 1, wherein the drug is chloramphenicol and the polymeric material is polyethylene terephthalate.
18. The medication-dispensing tablet as defined by claim 1, wherein the drug is promethazine trichloroacetate and the polymeric material is polyvinyl chloride.
19 The medication-dispensing tablet as defined by claim 1, wherein the drug is ehloramphenicol and the polymeric material is polydimethylsiloxane rubber.
20. The medication-dispening tablet as defined by claim 1, wherein the drug is a member selected from the group consisting of pilocarpine and pilocarpine perfiuorbutyrate and the polymeric material is polyvinyl chloride.
21. The medication-dispensing tablet as defined by claim 1, wherein the drug is dexamethasone and the polymeric material is nylon-66.
K i t i UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3 8, 0 Dated November 9, 1971 Inventor(s) Richard A. Ness It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:
Column 1, line 8, "ophtahalmic" should read ophthalmic-; line 20, "gylcerinated" should read -glycerinated-; line 64, "its" should read it--; line 70, "radically" should read -radially-. Column 2, line 16, "during" should read drug-; line 50, "terephtahalate" should read terephthalate.
Column 3, line 13, "chlortetracycleine" should read --chlortetracycline; line 31, "Sypathomimetics" should read Sympathomimetics-; line 35, following the word "sulfate" insert a comma; line 69, "nylon-plasticized" should read nylon-66 plasticized-; line 75, "in", second occurrence,
should read -it-. Column 4, line 2, "used" should read use-; line 31, "FIG." should read -FIGS.-; line 50, after "insert" add of-; line 51, "dow" should read Dow--; line 55, "to" should read and. Claim 1, line 12, delete the hyphen between "continuous" and "surfaced". Claim 1, line 27, insert thereto, drug-- between "drug" and "leaving".
Claim 7, line 2, insert or between "plasticized" and "unplasticized". Claim 7, line 7, after "polyvinyl delete "acetate." and insert alcohol, and cross-linked partially hydrolyzed polyvinyl acetate.--. Claim 20, line 47, "perfluorbutyrate" should read perfluorobutyrate.
In all the claims, each occurrence, delete the hyphen between "medication" and "dispensing".
Signed and sealed this 2nd day of May 1972.
EM F'O-1050 (10-69) (SEAL) Attest:
EDWARD M.FLE'I'CHER, JR. 5055111 Li-U'l'l'SUtiJ-LLK Attesting Officer Co missioner of Patents USCOMM-DC 6O376-F69 U S GOVERNMENT PRINHNG OFFICE 1969 0-366-334

Claims (20)

1. A medication-dispensing tablet for a human eyeball, said tablet comprising a reservoir of drug formulation confined within a flexible, imperforate and continuous-surfaced body of nonallergenic polymeric material which is insoluble in tear liquid, said body being formed of a drug-release rate-controlling polymer to continuously meter the flow of drug by diffusion from the reservoir to the eye at a controlled, predetermined and reproducible rate over a prolonged period of time, said body being adapted for insertion into the cul-de-sac of the conjunctiva between the sclera of the eyeball and eyelid, to be held in place against the eyeball by the pressure of the lid, and said body having a marginal outline and cross section adapted to assume essentially the configuration of the scleral curvature; said drug being capable of transport through the unbroken walls of said body by diffusion and said body being so constructed and arranged that, when applied to the eyeball, to dispense said drug thereto, drug leaving said body by diffusion is transported to the eyeball by the flow of tears and by the blinking action of the eyelids.
2. The medication-dispensing tablet as defined by claim 1, wherein the reservoir of drug formulation is comprised of a sealed container with walls of said polymeric material and said drug is contained in an interior chamber thereof.
3. The medication-dispensing tablet as defined by claim 2, wherein said polymeric material is selected from the group consisting of plasticized or unplasticized polyvinyl chloride, plasticized nylon, unplasticized soft nylon, plasticized polyethylene terephthalate, silicone rubber, hydrophilic hydrogel of an ester of acrylic or methacrylic acid, modified collagen, cross-linked hydrophilic polyether gel, cross-linked polyvinyl alcohol, and cross-linked partially hydrolyzed polyvinyl acetate.
4. The medication-dispensing tablet as defined by claim 3, wherein said polymeric material is silicone rubber.
5. The medication-dispensing tablet as defined by claim 3, wherein said polymeric material is a hydrophilic hydrogel of an ester of acrylic or methacrylic acid.
6. The medication-dispensing tablet as defined by claim 1, wherein the reservoir of drug formulation is comprised of a matrix of the drug-release rate-controlling polymeric material, said matrix having the drug distributed therethrough.
7. The medication-dispensing tablet as defined by claim 1, wherein said polymeric material is selected from the group consisting of plasticized unplasticized polyvinyl chloride, plasticized nylon, unplasticized soft nylon, plasticized polyethylene terephthalate, silicone rubber, hydrophilic hydrogel of an ester of acrylic or methacrylic acid, modified collagen, cross-linked hydrophilic polyether gel, cross-linked polyvinyl alcohol, and cross-linked partially hydrolyzed polyvinyl acetate.
8. The medication-dispensing tablet as defined by claim 7, wherein said polymeric material is silicone rubber.
9. The medication-dispensing tablet as defined by claim 7, wherein said polymeric material is a hydrophilic hydrogel of an ester of acrylic or methacrylic acid.
10. The medication-dispensing tablet as defined by claim 1, wherein said drug is an ophthalmic drug.
11. The medication-dispensing tablet as defined by claim 1, wherein said drug is a systemically active drug which will pass through the eye to the bloodstream and produce a pharmacologic response at a site remote from the eye.
12. The medication-dispensing tablet as defined by claim 1, wherein said drug is a systemically active drug which will pass through the tissue surrounding the eye to the bloodstream and produce a pharmacologic response at a site remote from the eye.
13. The medication-dispensing tablet as defined by claim 1, wherein from 1 microgram to 1 milligram of drug is incorporated in said tablet.
14. The medication-dispensing tablet as defined by claim 1, wherein same is circular in cross section and tapered at its ends.
15. The medication-dispensing tablet as defined by claim 1, wherein same is ellipsoidal in cross section and tapered at its ends.
16. The medication-dispensing tablet as defined by claim 1, wherein same ranges from 4 to 20 millimeters in length, 1 to 12 millimeters in width, and 0.1 to 1 millimeter in thickness.
17. The medication-dispensing tablet as defined by claim 1, wherein the drug is chloramphenicol and the polymeric material is polyethylene terephthalate.
18. The medication-dispensing tablet as defined by claim 1, wherein the drug is promethazine trichloroacetate and the polymeric material is polyvinyl chloride. 19 The medication-dispensing tablet as defined by claim 1, wherein the drug is chloramphenicol and the polymeric material is polydimethylsiloxane rubber.
20. The medication-dispensing tablet as defined by claim 1, wherein the drug is a member selected from the group consisting of pilocarpine and pilocarpine perfluorobutyrate and the polymeric material is polyvinyl chloride.
21. The medication-dispensing tablet as defined by claim 1, wherein the drug is dexamethasone and the polymeric material is nylon-66.
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Cited By (115)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3710796A (en) * 1971-05-14 1973-01-16 C Neefe Corneal drug delivery method
DE2243986A1 (en) * 1971-09-09 1973-03-29 Alza Corp BIODEGRADABLE EYE INSERT FOR ADMINISTRATION OF A MEDICINAL PRODUCT
US3811444A (en) * 1972-12-27 1974-05-21 Alza Corp Bioerodible ocular device
US3826258A (en) * 1972-02-07 1974-07-30 S Abraham Gradual release medicine carrier
US3828777A (en) * 1971-11-08 1974-08-13 Alza Corp Microporous ocular device
US3868445A (en) * 1972-11-30 1975-02-25 Pharmacia Ab Dosage unit containing a substance showing a topical effect on the eye, and a method of preparing same
US3870791A (en) * 1972-04-24 1975-03-11 Heskel M Haddad Solid state ophthalmic medication delivery method
US3914402A (en) * 1973-06-14 1975-10-21 Alza Corp Ophthalmic dosage form, for releasing medication over time
US3926188A (en) * 1974-11-14 1975-12-16 Alza Corp Laminated drug dispenser
USB520277I5 (en) * 1971-09-09 1976-02-17
US3957049A (en) * 1973-10-09 1976-05-18 Neefe Charles W Rechargeable drug delivery method
US3960150A (en) * 1971-09-09 1976-06-01 Alza Corporation Bioerodible ocular device
US3961628A (en) * 1974-04-10 1976-06-08 Alza Corporation Ocular drug dispensing system
US3981303A (en) * 1971-09-09 1976-09-21 Alza Corporation Bioerodible ocular device
US3985897A (en) * 1973-12-21 1976-10-12 Mead Johnson & Company Ocular hypotensive process employing dextrorotatory sulfonamidophenethanolamines
US3986510A (en) * 1971-09-09 1976-10-19 Alza Corporation Bioerodible ocular device
US3993071A (en) * 1971-09-09 1976-11-23 Alza Corporation Bioerodible ocular device
US3993073A (en) * 1969-04-01 1976-11-23 Alza Corporation Novel drug delivery device
US4008719A (en) * 1976-02-02 1977-02-22 Alza Corporation Osmotic system having laminar arrangement for programming delivery of active agent
US4014334A (en) * 1976-02-02 1977-03-29 Alza Corporation Laminated osmotic system for dispensing beneficial agent
US4144317A (en) * 1975-05-30 1979-03-13 Alza Corporation Device consisting of copolymer having acetoxy groups for delivering drugs
US4177256A (en) * 1973-04-25 1979-12-04 Alza Corporation Osmotic bursting drug delivery device
US4190642A (en) * 1978-04-17 1980-02-26 Alza Corporation Ocular therapeutic system for dispensing a medication formulation
US4281654A (en) * 1980-04-07 1981-08-04 Alza Corporation Drug delivery system for controlled ocular therapy
US4304226A (en) * 1980-03-03 1981-12-08 The Procter & Gamble Company Vaginal contraceptive
US4344431A (en) * 1969-03-24 1982-08-17 University Of Delaware Polymeric article for dispensing drugs
WO1984004680A1 (en) * 1983-05-25 1984-12-06 Alcon Lab Inc Ophthalmic gel
WO1984004681A1 (en) * 1983-05-25 1984-12-06 Alcon Lab Inc Ophthalmic solution
EP0212959A2 (en) * 1985-08-16 1987-03-04 BAUSCH & LOMB INCORPORATED Sustained-release formulation containing an amin acid polymer with a lower alkyl (C1-C4) polar solvent
EP0219208A2 (en) * 1985-08-16 1987-04-22 BAUSCH & LOMB INCORPORATED Substained-release formulation containing an amino acid polymer
US4660546A (en) * 1984-11-07 1987-04-28 Robert S. Herrick Method for treating for deficiency of tears
EP0219207A3 (en) * 1985-08-16 1988-06-01 Bausch & Lomb Incorporated Sustained-release formulation comprising a hydrophobic polymer system
US4959217A (en) * 1986-05-22 1990-09-25 Syntex (U.S.A.) Inc. Delayed/sustained release of macromolecules
EP0411578A1 (en) * 1989-08-01 1991-02-06 Terumo Kabushiki Kaisha Liquid applicator
US5185152A (en) * 1990-01-10 1993-02-09 Peyman Gholam A Method and apparatus for controlled release drug delivery to the cornea and anterior chamber of the eye
WO1993019707A1 (en) * 1992-04-02 1993-10-14 Bausch & Lomb Incorporated Ophthalmic article
US5378475A (en) * 1991-02-21 1995-01-03 University Of Kentucky Research Foundation Sustained release drug delivery devices
US5660851A (en) * 1989-12-26 1997-08-26 Yissum Research Development Company Of The Hebrew Univ. Of Jerusalem Ocular inserts
EP0863729A1 (en) * 1995-09-27 1998-09-16 Control Delivery Systems, Inc. Implantable controlled release device to deliver drugs directly to an internal portion of the body
US5902598A (en) * 1997-08-28 1999-05-11 Control Delivery Systems, Inc. Sustained release drug delivery devices
US5928662A (en) * 1996-07-31 1999-07-27 Phillips; Andrew F. Ocular drug delivery device
US6123957A (en) * 1997-07-16 2000-09-26 Jernberg; Gary R. Delivery of agents and method for regeneration of periodontal tissues
WO2000062760A1 (en) 1999-04-19 2000-10-26 Eyelab Group, Llc Ophthalmic insert and method for sustained release of medication to the eye
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
US20020106395A1 (en) * 2001-01-03 2002-08-08 Brubaker Michael J. Sustained release drug delivery devices with prefabricated permeable plugs
US20020110635A1 (en) * 2001-01-26 2002-08-15 Brubaker Michael J. Process for the production of sustained release drug delivery devices
WO2002064071A1 (en) * 2001-02-13 2002-08-22 The Lions Eye Institute Of Western Australia Device and method for anterior segment drug delivery
US20020188282A1 (en) * 2001-02-13 2002-12-12 Robert Greenberg Implantable drug delivery device
US20020198453A1 (en) * 2001-06-11 2002-12-26 Herrick Family Limited Partnership Implant capable of forming a differential image in an eye and methods of inserting and locating same
US20030021828A1 (en) * 1999-03-22 2003-01-30 Control Delivery Systems Method for treating and/or preventing retinal diseases with substained release corticosteroids
WO2003096876A2 (en) * 2001-04-01 2003-11-27 Sommer Phillipe L Continuously operational diagnostic device
US20040034357A1 (en) * 1999-08-03 2004-02-19 University Of Massachusetts, A Massachusetts Corporation Controlled release implantable devices
US6756058B2 (en) 2001-01-03 2004-06-29 Bausch & Lomb Incorporated Sustained release drug delivery devices with multiple agents
US6756049B2 (en) 2000-12-29 2004-06-29 Bausch & Lomb Incorporated Sustained release drug delivery devices
US20050027312A1 (en) * 2001-08-10 2005-02-03 Andreas Hahn Balloon occlusion device
US20060134176A1 (en) * 2004-12-22 2006-06-22 Bausch & Lomb Incorporated Pharmaceutical delivery system and method of use
US20060198892A1 (en) * 2003-08-22 2006-09-07 Ellis Jeanne Y Polymeric systems for controlled drug therapy
US20060270968A1 (en) * 2003-03-21 2006-11-30 Robert Greenberg Transretinal implant and method of manufacture
US20070112318A1 (en) * 2003-08-26 2007-05-17 Leahy Charles D Ocular drug delivery device
US20070190111A1 (en) * 2001-03-15 2007-08-16 Govemment Of The U.S.A, Represented By The Secretary, Department. Of Health And Human Ocular therapeutic agent delivery devices and methods for making and using such devices
US20080086101A1 (en) * 2006-08-25 2008-04-10 David Freilich Ophthalmic insert
US20080171072A1 (en) * 2006-08-11 2008-07-17 Frank Burczynski Ocular inserts containing apomorphine
US20090004245A1 (en) * 2007-06-28 2009-01-01 Orilla Werhner C Use of an iris simulated layer to allow aesthetic appearance drug loaded contact lens
US20090004244A1 (en) * 2007-06-27 2009-01-01 Orilla Werhner C Iris design as a drug depot for zonal drug delivery by contact lens
US20090162417A1 (en) * 2007-12-21 2009-06-25 Cook Incorporated Drug eluting ocular conformer
US7563255B2 (en) 2001-05-03 2009-07-21 Massachusetts Eye And Ear Infirmary Implantable drug delivery device and use thereof
US20100069857A1 (en) * 2008-09-18 2010-03-18 Oasis Research LLC Ring Shaped Contoured Collagen Shield For Ophthalmic Drug Delivery
WO2010093873A2 (en) 2009-02-12 2010-08-19 Incept, Llc Drug delivery through hydrogel plugs
US20100239637A1 (en) * 2008-12-11 2010-09-23 Massachusetts Institute Of Technology Contact lens drug delivery device
WO2011123180A1 (en) 2010-04-03 2011-10-06 Praful Doshi Medical devices including medicaments and methods of making and using same
US8133501B2 (en) 2002-02-08 2012-03-13 Boston Scientific Scimed, Inc. Implantable or insertable medical devices for controlled drug delivery
WO2012033730A2 (en) 2010-09-08 2012-03-15 Johnson & Johnson Vision Care, Inc. Punctal plug containing drug formulation
WO2012037330A1 (en) 2010-09-17 2012-03-22 Johnson & Johnson Vision Care, Inc. Punctal plugs with directional release
WO2012082486A1 (en) 2010-12-16 2012-06-21 Johnson & Johnson Vision Care, Inc. Punctal plug with drug core retention features
US8277830B2 (en) 2009-01-29 2012-10-02 Forsight Vision4, Inc. Posterior segment drug delivery
WO2012154427A1 (en) 2011-05-06 2012-11-15 Johnson & Johnson Vision Care, Inc. Punctal plugs for controlled release of therapeutic agents
US8486052B2 (en) 2001-06-12 2013-07-16 The Johns Hopkins University School Of Medicine Reservoir device for intraocular drug delivery
EP2633840A2 (en) 2012-02-29 2013-09-04 Johnson & Johnson Vision Care, Inc. Punctal plug with energized containment array
US8623395B2 (en) 2010-01-29 2014-01-07 Forsight Vision4, Inc. Implantable therapeutic device
US8685427B2 (en) 2002-07-31 2014-04-01 Boston Scientific Scimed, Inc. Controlled drug delivery
US8715712B2 (en) 2011-09-14 2014-05-06 Forsight Vision5, Inc. Ocular insert apparatus and methods
US8765166B2 (en) 2010-05-17 2014-07-01 Novaer Holdings, Inc. Drug delivery devices for delivery of ocular therapeutic agents
US8871241B2 (en) 2002-05-07 2014-10-28 Psivida Us, Inc. Injectable sustained release delivery devices
US8905963B2 (en) 2010-08-05 2014-12-09 Forsight Vision4, Inc. Injector apparatus and method for drug delivery
US8920826B2 (en) 2002-07-31 2014-12-30 Boston Scientific Scimed, Inc. Medical imaging reference devices
US9005649B2 (en) 2009-07-14 2015-04-14 Board Of Regents, The University Of Texas System Methods for making controlled delivery devices having zero order kinetics
WO2015071427A1 (en) 2013-11-14 2015-05-21 Eyed Pharma Eye device
US9102105B2 (en) 2011-09-13 2015-08-11 Vista Scientific Llc Method for forming an ocular drug delivery device
WO2015164563A1 (en) 2014-04-25 2015-10-29 Johnson & Johnson Vision Care, Inc. Method and ophthalmic device with active agent release system
US9421126B2 (en) 2009-06-03 2016-08-23 Forsight Vision5, Inc. Anterior segment drug delivery
US9474756B2 (en) 2014-08-08 2016-10-25 Forsight Vision4, Inc. Stable and soluble formulations of receptor tyrosine kinase inhibitors, and methods of preparation thereof
US9492315B2 (en) 2010-08-05 2016-11-15 Forsight Vision4, Inc. Implantable therapeutic device
US9526654B2 (en) 2013-03-28 2016-12-27 Forsight Vision4, Inc. Ophthalmic implant for delivering therapeutic substances
US9750636B2 (en) 2012-10-26 2017-09-05 Forsight Vision5, Inc. Ophthalmic system for sustained release of drug to eye
US9883968B2 (en) 2011-09-16 2018-02-06 Forsight Vision4, Inc. Fluid exchange apparatus and methods
US9968603B2 (en) 2013-03-14 2018-05-15 Forsight Vision4, Inc. Systems for sustained intraocular delivery of low solubility compounds from a port delivery system implant
WO2018119188A2 (en) 2016-12-21 2018-06-28 Johnson & Johnson Vision Care, Inc. Extended period timer circuits for ophthalmic devices
US10010502B2 (en) 2015-05-19 2018-07-03 Amorphex Therapeutics Llc Device that delivers a sustained low-dose of a myopia-suppressing drug, while preserving pupillary function and accommodation
US10010448B2 (en) 2012-02-03 2018-07-03 Forsight Vision4, Inc. Insertion and removal methods and apparatus for therapeutic devices
US10098836B2 (en) 2013-05-02 2018-10-16 Retina Foundation Of The Southwest Method for forming a molded two-layer ocular implant
US10166142B2 (en) 2010-01-29 2019-01-01 Forsight Vision4, Inc. Small molecule delivery with implantable therapeutic device
US10172740B2 (en) 2015-11-06 2019-01-08 David E Freilich Lacrimal stent
US10258503B2 (en) 2014-07-15 2019-04-16 Forsight Vision4, Inc. Ocular implant delivery device and method
US10398592B2 (en) 2011-06-28 2019-09-03 Forsight Vision4, Inc. Diagnostic methods and apparatus
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
US10500091B2 (en) 2014-11-10 2019-12-10 Forsight Vision4, Inc. Expandable drug delivery devices and methods of use
US10617557B2 (en) 2010-08-05 2020-04-14 Forsight Vision4, Inc. Combined drug delivery methods and apparatus
US10874548B2 (en) 2010-11-19 2020-12-29 Forsight Vision4, Inc. Therapeutic agent formulations for implanted devices
US11224602B2 (en) 2015-04-13 2022-01-18 Forsight Vision5, Inc. Ocular insert composition of a semi-crystalline or crystalline pharmaceutically active agent
US11351058B2 (en) 2017-03-17 2022-06-07 W. L. Gore & Associates, Inc. Glaucoma treatment systems and methods
US11419759B2 (en) 2017-11-21 2022-08-23 Forsight Vision4, Inc. Fluid exchange apparatus for expandable port delivery system and methods of use
US11432959B2 (en) 2015-11-20 2022-09-06 Forsight Vision4, Inc. Porous structures for extended release drug delivery devices
US11617644B2 (en) 2014-10-13 2023-04-04 W. L. Gore & Associates, Inc. Prosthetic valved conduit
US11617680B2 (en) 2016-04-05 2023-04-04 Forsight Vision4, Inc. Implantable ocular drug delivery devices
US11678983B2 (en) 2018-12-12 2023-06-20 W. L. Gore & Associates, Inc. Implantable component with socket

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3220960A (en) * 1960-12-21 1965-11-30 Wichterle Otto Cross-linked hydrophilic polymers and articles made therefrom
US3339546A (en) * 1963-12-13 1967-09-05 Squibb & Sons Inc Bandage for adhering to moist surfaces
US3416530A (en) * 1966-03-02 1968-12-17 Richard A. Ness Eyeball medication dispensing tablet

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3220960A (en) * 1960-12-21 1965-11-30 Wichterle Otto Cross-linked hydrophilic polymers and articles made therefrom
US3339546A (en) * 1963-12-13 1967-09-05 Squibb & Sons Inc Bandage for adhering to moist surfaces
US3416530A (en) * 1966-03-02 1968-12-17 Richard A. Ness Eyeball medication dispensing tablet

Cited By (205)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4344431A (en) * 1969-03-24 1982-08-17 University Of Delaware Polymeric article for dispensing drugs
US3993073A (en) * 1969-04-01 1976-11-23 Alza Corporation Novel drug delivery device
US3710796A (en) * 1971-05-14 1973-01-16 C Neefe Corneal drug delivery method
US3960150A (en) * 1971-09-09 1976-06-01 Alza Corporation Bioerodible ocular device
DE2243986A1 (en) * 1971-09-09 1973-03-29 Alza Corp BIODEGRADABLE EYE INSERT FOR ADMINISTRATION OF A MEDICINAL PRODUCT
FR2157798A1 (en) * 1971-09-09 1973-06-08 Alza Corp
US3995635A (en) * 1971-09-09 1976-12-07 Alza Corporation Ocular insert
US3993071A (en) * 1971-09-09 1976-11-23 Alza Corporation Bioerodible ocular device
US3986510A (en) * 1971-09-09 1976-10-19 Alza Corporation Bioerodible ocular device
US3981303A (en) * 1971-09-09 1976-09-21 Alza Corporation Bioerodible ocular device
USB520277I5 (en) * 1971-09-09 1976-02-17
US3828777A (en) * 1971-11-08 1974-08-13 Alza Corp Microporous ocular device
US3826258A (en) * 1972-02-07 1974-07-30 S Abraham Gradual release medicine carrier
US3870791A (en) * 1972-04-24 1975-03-11 Heskel M Haddad Solid state ophthalmic medication delivery method
US3868445A (en) * 1972-11-30 1975-02-25 Pharmacia Ab Dosage unit containing a substance showing a topical effect on the eye, and a method of preparing same
US3811444A (en) * 1972-12-27 1974-05-21 Alza Corp Bioerodible ocular device
US4177256A (en) * 1973-04-25 1979-12-04 Alza Corporation Osmotic bursting drug delivery device
US3914402A (en) * 1973-06-14 1975-10-21 Alza Corp Ophthalmic dosage form, for releasing medication over time
US3957049A (en) * 1973-10-09 1976-05-18 Neefe Charles W Rechargeable drug delivery method
US3985897A (en) * 1973-12-21 1976-10-12 Mead Johnson & Company Ocular hypotensive process employing dextrorotatory sulfonamidophenethanolamines
US3961628A (en) * 1974-04-10 1976-06-08 Alza Corporation Ocular drug dispensing system
US3926188A (en) * 1974-11-14 1975-12-16 Alza Corp Laminated drug dispenser
US4144317A (en) * 1975-05-30 1979-03-13 Alza Corporation Device consisting of copolymer having acetoxy groups for delivering drugs
US4116241A (en) * 1976-02-02 1978-09-26 Alza Corporation Osmotic system with laminated wall comprising structurally different semipermeable lamina
US4014334A (en) * 1976-02-02 1977-03-29 Alza Corporation Laminated osmotic system for dispensing beneficial agent
US4008719A (en) * 1976-02-02 1977-02-22 Alza Corporation Osmotic system having laminar arrangement for programming delivery of active agent
US4190642A (en) * 1978-04-17 1980-02-26 Alza Corporation Ocular therapeutic system for dispensing a medication formulation
US4304226A (en) * 1980-03-03 1981-12-08 The Procter & Gamble Company Vaginal contraceptive
US4281654A (en) * 1980-04-07 1981-08-04 Alza Corporation Drug delivery system for controlled ocular therapy
WO1984004681A1 (en) * 1983-05-25 1984-12-06 Alcon Lab Inc Ophthalmic solution
WO1984004680A1 (en) * 1983-05-25 1984-12-06 Alcon Lab Inc Ophthalmic gel
US4660546A (en) * 1984-11-07 1987-04-28 Robert S. Herrick Method for treating for deficiency of tears
EP0212959A2 (en) * 1985-08-16 1987-03-04 BAUSCH & LOMB INCORPORATED Sustained-release formulation containing an amin acid polymer with a lower alkyl (C1-C4) polar solvent
EP0219208A2 (en) * 1985-08-16 1987-04-22 BAUSCH & LOMB INCORPORATED Substained-release formulation containing an amino acid polymer
EP0219207A3 (en) * 1985-08-16 1988-06-01 Bausch & Lomb Incorporated Sustained-release formulation comprising a hydrophobic polymer system
EP0219208A3 (en) * 1985-08-16 1988-06-01 Bausch & Lomb Incorporated Substained-release formulation containing an amino acid polymer
EP0212959A3 (en) * 1985-08-16 1988-06-01 Bausch & Lomb Incorporated Sustained-release formulation containing an amin acid polymer with a lower alkyl (c1-c4) polar solvent
US4959217A (en) * 1986-05-22 1990-09-25 Syntex (U.S.A.) Inc. Delayed/sustained release of macromolecules
EP0411578A1 (en) * 1989-08-01 1991-02-06 Terumo Kabushiki Kaisha Liquid applicator
US5054948A (en) * 1989-08-01 1991-10-08 Terumo Kabushiki Kaisha Liquid applicator
US5660851A (en) * 1989-12-26 1997-08-26 Yissum Research Development Company Of The Hebrew Univ. Of Jerusalem Ocular inserts
US5185152A (en) * 1990-01-10 1993-02-09 Peyman Gholam A Method and apparatus for controlled release drug delivery to the cornea and anterior chamber of the eye
US5378475A (en) * 1991-02-21 1995-01-03 University Of Kentucky Research Foundation Sustained release drug delivery devices
WO1993019707A1 (en) * 1992-04-02 1993-10-14 Bausch & Lomb Incorporated Ophthalmic article
EP0863729B1 (en) * 1995-09-27 2004-12-08 Control Delivery Systems, Inc. Implantable controlled release device to deliver drugs directly to an internal portion of the body
EP0863729A1 (en) * 1995-09-27 1998-09-16 Control Delivery Systems, Inc. Implantable controlled release device to deliver drugs directly to an internal portion of the body
US5928662A (en) * 1996-07-31 1999-07-27 Phillips; Andrew F. Ocular drug delivery device
US6123957A (en) * 1997-07-16 2000-09-26 Jernberg; Gary R. Delivery of agents and method for regeneration of periodontal tissues
US5902598A (en) * 1997-08-28 1999-05-11 Control Delivery Systems, Inc. Sustained release drug delivery devices
US6196993B1 (en) 1998-04-20 2001-03-06 Eyelab Group, Llc Ophthalmic insert and method for sustained release of medication to the eye
US20100168073A1 (en) * 1999-03-22 2010-07-01 Paul Ashton Method for treating and/or preventing retinal diseases with sustained release corticosteroids
US8252307B2 (en) 1999-03-22 2012-08-28 Psivida Us, Inc. Method for treating and/or preventing retinal diseases with sustained release corticosteroids
US20030021828A1 (en) * 1999-03-22 2003-01-30 Control Delivery Systems Method for treating and/or preventing retinal diseases with substained release corticosteroids
WO2000062760A1 (en) 1999-04-19 2000-10-26 Eyelab Group, Llc Ophthalmic insert and method for sustained release of medication to the eye
US20040034357A1 (en) * 1999-08-03 2004-02-19 University Of Massachusetts, A Massachusetts Corporation Controlled release implantable devices
US8574659B2 (en) 2000-04-26 2013-11-05 Psivida Us, Inc. Sustained release drug delivery devices, methods of use, and methods of manufacturing thereof
US8574613B2 (en) 2000-04-26 2013-11-05 Psivida Us, Inc. Sustained release drug delivery devices, methods of use, and methods of manufacturing thereof
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
US9849085B2 (en) 2000-04-26 2017-12-26 Psivida Us Inc. Sustained release drug delivery devices, methods of use, and methods of manufacturing thereof
EP1982701A2 (en) 2000-04-26 2008-10-22 pSivida Inc Sustained Release Drug Delivery Devices, Methods of Use, and Methods of Manufacturing Thereof
US9192579B2 (en) 2000-04-26 2015-11-24 Psivida Us, Inc. Sustained release drug delivery devices, methods of use, and methods of manufacturing thereof
US6756049B2 (en) 2000-12-29 2004-06-29 Bausch & Lomb Incorporated Sustained release drug delivery devices
US20040208909A1 (en) * 2000-12-29 2004-10-21 Brubaker Michael J Sustained release drug delivery devices
US6756058B2 (en) 2001-01-03 2004-06-29 Bausch & Lomb Incorporated Sustained release drug delivery devices with multiple agents
US20020106395A1 (en) * 2001-01-03 2002-08-08 Brubaker Michael J. Sustained release drug delivery devices with prefabricated permeable plugs
US6964781B2 (en) 2001-01-03 2005-11-15 Bausch & Lomb Incorporated Sustained release drug delivery devices with prefabricated permeable plugs
US6991808B2 (en) 2001-01-26 2006-01-31 Bausch & Lomb Inc. Process for the production of sustained release drug delivery devices
US20060062826A1 (en) * 2001-01-26 2006-03-23 Brubaker Michael J Process for the production of sustained release drug delivery devices
US20020110635A1 (en) * 2001-01-26 2002-08-15 Brubaker Michael J. Process for the production of sustained release drug delivery devices
WO2002064071A1 (en) * 2001-02-13 2002-08-22 The Lions Eye Institute Of Western Australia Device and method for anterior segment drug delivery
US20070026048A1 (en) * 2001-02-13 2007-02-01 Robert Greenberg Implantable drug delivery device
US7181287B2 (en) 2001-02-13 2007-02-20 Second Sight Medical Products, Inc. Implantable drug delivery device
US20020188282A1 (en) * 2001-02-13 2002-12-12 Robert Greenberg Implantable drug delivery device
US7527621B2 (en) 2001-02-13 2009-05-05 Second Sight Medical Products, Inc. Implantable drug delivery device
US20100272777A1 (en) * 2001-03-15 2010-10-28 The Government Of The United States Of America, As Represented By The Secretary, Ocular therapeutic agent delivery devices and methdos for making and using such devices
US20070190111A1 (en) * 2001-03-15 2007-08-16 Govemment Of The U.S.A, Represented By The Secretary, Department. Of Health And Human Ocular therapeutic agent delivery devices and methods for making and using such devices
WO2003096876A2 (en) * 2001-04-01 2003-11-27 Sommer Phillipe L Continuously operational diagnostic device
WO2003096876A3 (en) * 2001-04-01 2004-03-25 Phillipe L Sommer Continuously operational diagnostic device
US7563255B2 (en) 2001-05-03 2009-07-21 Massachusetts Eye And Ear Infirmary Implantable drug delivery device and use thereof
US7404825B2 (en) 2001-06-11 2008-07-29 Herrick Ii Robert S Implant capable of forming a differential image in an eye
US20020198453A1 (en) * 2001-06-11 2002-12-26 Herrick Family Limited Partnership Implant capable of forming a differential image in an eye and methods of inserting and locating same
US20070135914A1 (en) * 2001-06-11 2007-06-14 Herrick Robert S Ii Implant capable of forming a differential image in an eye and methods of inserting and locating same
US20070299515A1 (en) * 2001-06-11 2007-12-27 Herrick Robert S Ii Implant capable of forming a differential image in an eye and methods of inserting and locating same
US10470924B2 (en) 2001-06-12 2019-11-12 The Johns Hopkins University Reservoir device for intraocular drug delivery
US9522082B2 (en) 2001-06-12 2016-12-20 The Johns Hopkins University Reservoir device for intraocular drug delivery
US8486052B2 (en) 2001-06-12 2013-07-16 The Johns Hopkins University School Of Medicine Reservoir device for intraocular drug delivery
US9180046B2 (en) 2001-06-12 2015-11-10 The Johns Hopkins University School Of Medicine Reservoir device for intraocular drug delivery
US20050027312A1 (en) * 2001-08-10 2005-02-03 Andreas Hahn Balloon occlusion device
US8133501B2 (en) 2002-02-08 2012-03-13 Boston Scientific Scimed, Inc. Implantable or insertable medical devices for controlled drug delivery
US8691264B2 (en) 2002-02-08 2014-04-08 Boston Scientific Scimed, Inc. Implantable or insertable medical devices for controlled drug delivery
US8871241B2 (en) 2002-05-07 2014-10-28 Psivida Us, Inc. Injectable sustained release delivery devices
US8685427B2 (en) 2002-07-31 2014-04-01 Boston Scientific Scimed, Inc. Controlled drug delivery
US8920826B2 (en) 2002-07-31 2014-12-30 Boston Scientific Scimed, Inc. Medical imaging reference devices
US9993367B2 (en) 2003-03-21 2018-06-12 Second Sight Medical Products, Inc. Transretinal implant and method of manufacture
US20060270968A1 (en) * 2003-03-21 2006-11-30 Robert Greenberg Transretinal implant and method of manufacture
US20060198892A1 (en) * 2003-08-22 2006-09-07 Ellis Jeanne Y Polymeric systems for controlled drug therapy
US20100178315A1 (en) * 2003-08-22 2010-07-15 Vista Scientific Llc Polymeric systems for controlled drug therapy
US8167855B2 (en) 2003-08-26 2012-05-01 Vista Scientific Llc Ocular drug delivery device
US20070112318A1 (en) * 2003-08-26 2007-05-17 Leahy Charles D Ocular drug delivery device
US8287504B2 (en) 2003-08-26 2012-10-16 Vista Scientific Llc Ocular drug delivery device
US8679078B2 (en) 2003-08-26 2014-03-25 Vista Scientific Llc Ocular drug delivery device
US20100331796A1 (en) * 2003-08-26 2010-12-30 Vista Scientific Llc Ocular drug delivery device
US20060134176A1 (en) * 2004-12-22 2006-06-22 Bausch & Lomb Incorporated Pharmaceutical delivery system and method of use
US20080171072A1 (en) * 2006-08-11 2008-07-17 Frank Burczynski Ocular inserts containing apomorphine
US20080086101A1 (en) * 2006-08-25 2008-04-10 David Freilich Ophthalmic insert
US20090004244A1 (en) * 2007-06-27 2009-01-01 Orilla Werhner C Iris design as a drug depot for zonal drug delivery by contact lens
US20090004245A1 (en) * 2007-06-28 2009-01-01 Orilla Werhner C Use of an iris simulated layer to allow aesthetic appearance drug loaded contact lens
US20090162417A1 (en) * 2007-12-21 2009-06-25 Cook Incorporated Drug eluting ocular conformer
US20100069857A1 (en) * 2008-09-18 2010-03-18 Oasis Research LLC Ring Shaped Contoured Collagen Shield For Ophthalmic Drug Delivery
US7985208B2 (en) * 2008-09-18 2011-07-26 Oasis Research LLC Ring shaped contoured collagen shield for ophthalmic drug delivery
US8414912B2 (en) 2008-12-11 2013-04-09 Massachusetts Institute Of Technology Contact lens drug delivery device
US20100239637A1 (en) * 2008-12-11 2010-09-23 Massachusetts Institute Of Technology Contact lens drug delivery device
US8277830B2 (en) 2009-01-29 2012-10-02 Forsight Vision4, Inc. Posterior segment drug delivery
US9417238B2 (en) 2009-01-29 2016-08-16 Forsight Vision4, Inc. Posterior segment drug delivery
US11642310B2 (en) 2009-01-29 2023-05-09 Forsight Vision4, Inc. Posterior segment drug delivery
US9851351B2 (en) 2009-01-29 2017-12-26 Forsight Vision4, Inc. Posterior segment drug delivery
US10656152B2 (en) 2009-01-29 2020-05-19 Forsight Vision4, Inc. Posterior segment drug delivery
US8795712B2 (en) 2009-01-29 2014-08-05 Forsight Vision4, Inc. Posterior segment drug delivery
US8808727B2 (en) 2009-01-29 2014-08-19 Forsight Vision4, Inc. Posterior segment drug delivery
US8298578B2 (en) 2009-01-29 2012-10-30 Forsight Vision4, Inc. Posterior segment drug delivery
US8399006B2 (en) 2009-01-29 2013-03-19 Forsight Vision4, Inc. Posterior segment drug delivery
US9066779B2 (en) 2009-01-29 2015-06-30 Forsight Vision4, Inc. Implantable therapeutic device
US10813788B2 (en) 2009-01-29 2020-10-27 Forsight Vision4, Inc. Implantable therapeutic device
WO2010093873A2 (en) 2009-02-12 2010-08-19 Incept, Llc Drug delivery through hydrogel plugs
US10004636B2 (en) 2009-06-03 2018-06-26 Forsight Vision5, Inc. Anterior segment drug delivery
US9421126B2 (en) 2009-06-03 2016-08-23 Forsight Vision5, Inc. Anterior segment drug delivery
US10736774B2 (en) 2009-06-03 2020-08-11 Forsight Vision5, Inc. Anterior segment drug delivery
US9005649B2 (en) 2009-07-14 2015-04-14 Board Of Regents, The University Of Texas System Methods for making controlled delivery devices having zero order kinetics
US8623395B2 (en) 2010-01-29 2014-01-07 Forsight Vision4, Inc. Implantable therapeutic device
US10166142B2 (en) 2010-01-29 2019-01-01 Forsight Vision4, Inc. Small molecule delivery with implantable therapeutic device
US11077054B2 (en) 2010-04-03 2021-08-03 Praful Doshi Medical devices including medicaments and methods of making and using same including enhancing comfort, enhancing drug penetration, and treatment of myopia
EP3195858A1 (en) 2010-04-03 2017-07-26 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
US10369099B2 (en) 2010-04-03 2019-08-06 Praful Doshi Medical devices including medicaments and methods of making and using same
WO2011123180A1 (en) 2010-04-03 2011-10-06 Praful Doshi Medical devices including medicaments and methods of making and using same
US10842740B2 (en) 2010-04-03 2020-11-24 Praful Doshi Medical devices including medicaments and methods of making and using same including enhancing comfort, enhancing drug penetration, and treatment of myopia
US10188604B2 (en) 2010-04-03 2019-01-29 Praful Doshi Medical devices including medicaments and methods of making and using same
US9931296B2 (en) 2010-04-03 2018-04-03 Praful Doshi Medical devices including medicaments and methods of making and using same
US11234927B2 (en) 2010-04-03 2022-02-01 Praful Doshi Medical devices including medicaments and methods of making and using same including enhancing comfort, enhancing drug penetration, and treatment of myopia
US10076493B2 (en) 2010-04-03 2018-09-18 Praful Doshi Medical devices including medicaments and methods of making and using same
US10632068B2 (en) 2010-04-03 2020-04-28 Praful Doshi Medical devices including medicaments and methods of making and using same including enhancing comfort, enhancing drug penetration, and treatment of myopia
US10045938B2 (en) 2010-04-03 2018-08-14 Praful Doshi Medical devices including medicaments and methods of making and using same
US11510869B2 (en) 2010-04-03 2022-11-29 Praful Doshi Medical devices including medicaments and methods of making and using same including enhancing comfort, enhancing drug penetration, and treatment of myopia
US8765166B2 (en) 2010-05-17 2014-07-01 Novaer Holdings, Inc. Drug delivery devices for delivery of ocular therapeutic agents
US8939948B2 (en) 2010-06-01 2015-01-27 Forsight Vision5, Inc. Ocular insert apparatus and methods
US9937073B2 (en) 2010-06-01 2018-04-10 Forsight Vision5, Inc. Ocular insert apparatus and methods
US9492315B2 (en) 2010-08-05 2016-11-15 Forsight Vision4, Inc. Implantable therapeutic device
US11786396B2 (en) 2010-08-05 2023-10-17 Forsight Vision4, Inc. Injector apparatus and method for drug delivery
US10617557B2 (en) 2010-08-05 2020-04-14 Forsight Vision4, Inc. Combined drug delivery methods and apparatus
US10265215B2 (en) 2010-08-05 2019-04-23 Forsight Vision4, Inc. Injector apparatus and method for drug delivery
US9861521B2 (en) 2010-08-05 2018-01-09 Forsight Vision4, Inc. Injector apparatus and method for drug delivery
US11679027B2 (en) 2010-08-05 2023-06-20 Forsight Vision4, Inc. Combined drug delivery methods and apparatus
US9033911B2 (en) 2010-08-05 2015-05-19 Forsight Vision4, Inc. Injector apparatus and method for drug delivery
US8905963B2 (en) 2010-08-05 2014-12-09 Forsight Vision4, Inc. Injector apparatus and method for drug delivery
WO2012033730A2 (en) 2010-09-08 2012-03-15 Johnson & Johnson Vision Care, Inc. Punctal plug containing drug formulation
US8821457B2 (en) 2010-09-08 2014-09-02 Johnson & Johnson Vision Care, Inc. Punctal plug containing drug formulation
US8894602B2 (en) 2010-09-17 2014-11-25 Johnson & Johnson Vision Care, Inc. Punctal plugs with directional release
WO2012037330A1 (en) 2010-09-17 2012-03-22 Johnson & Johnson Vision Care, Inc. Punctal plugs with directional release
US11065151B2 (en) 2010-11-19 2021-07-20 Forsight Vision4, Inc. Therapeutic agent formulations for implanted devices
US10874548B2 (en) 2010-11-19 2020-12-29 Forsight Vision4, Inc. Therapeutic agent formulations for implanted devices
WO2012082486A1 (en) 2010-12-16 2012-06-21 Johnson & Johnson Vision Care, Inc. Punctal plug with drug core retention features
WO2012154427A1 (en) 2011-05-06 2012-11-15 Johnson & Johnson Vision Care, Inc. Punctal plugs for controlled release of therapeutic agents
US9301874B2 (en) 2011-05-06 2016-04-05 Johnson & Johnson Vision Care, Inc. Punctal plugs for controlled release of therapeutic agents
US10398592B2 (en) 2011-06-28 2019-09-03 Forsight Vision4, Inc. Diagnostic methods and apparatus
US11813196B2 (en) 2011-06-28 2023-11-14 Forsight Vision4, Inc. Diagnostic methods and apparatus
US9102105B2 (en) 2011-09-13 2015-08-11 Vista Scientific Llc Method for forming an ocular drug delivery device
US10835416B2 (en) 2011-09-14 2020-11-17 Forsight Vision5, Inc. Ocular insert apparatus and methods
US8715712B2 (en) 2011-09-14 2014-05-06 Forsight Vision5, Inc. Ocular insert apparatus and methods
US10653554B2 (en) 2011-09-16 2020-05-19 Forsight Vision4, Inc. Fluid exchange apparatus and methods
US9883968B2 (en) 2011-09-16 2018-02-06 Forsight Vision4, Inc. Fluid exchange apparatus and methods
US10010448B2 (en) 2012-02-03 2018-07-03 Forsight Vision4, Inc. Insertion and removal methods and apparatus for therapeutic devices
US10603209B2 (en) 2012-02-03 2020-03-31 Forsight Vision4, Inc. Insertion and removal methods and apparatus for therapeutic devices
EP2633840A2 (en) 2012-02-29 2013-09-04 Johnson & Johnson Vision Care, Inc. Punctal plug with energized containment array
US9750636B2 (en) 2012-10-26 2017-09-05 Forsight Vision5, Inc. Ophthalmic system for sustained release of drug to eye
US10456293B2 (en) 2012-10-26 2019-10-29 Forsight Vision5, Inc. Ophthalmic system for sustained release of drug to eye
US9968603B2 (en) 2013-03-14 2018-05-15 Forsight Vision4, Inc. Systems for sustained intraocular delivery of low solubility compounds from a port delivery system implant
US9526654B2 (en) 2013-03-28 2016-12-27 Forsight Vision4, Inc. Ophthalmic implant for delivering therapeutic substances
US10398593B2 (en) 2013-03-28 2019-09-03 Forsight Vision4, Inc. Ophthalmic implant for delivering therapeutic substances
US11510810B2 (en) 2013-03-28 2022-11-29 Forsight Vision4, Inc. Ophthalmic implant for delivering therapeutic substances
US10449145B2 (en) 2013-05-02 2019-10-22 Retina Foundation Of The Southwest Two-layer ocular implant
US10098836B2 (en) 2013-05-02 2018-10-16 Retina Foundation Of The Southwest Method for forming a molded two-layer ocular implant
US10881609B2 (en) 2013-05-02 2021-01-05 Retina Foundation Of The Southwest Methods for treating eye disorders using ocular implants
WO2015071427A1 (en) 2013-11-14 2015-05-21 Eyed Pharma Eye device
EP3566693A1 (en) 2013-11-14 2019-11-13 EyeD Pharma Eye device
WO2015164563A1 (en) 2014-04-25 2015-10-29 Johnson & Johnson Vision Care, Inc. Method and ophthalmic device with active agent release system
US10258503B2 (en) 2014-07-15 2019-04-16 Forsight Vision4, Inc. Ocular implant delivery device and method
US11337853B2 (en) 2014-07-15 2022-05-24 Forsight Vision4, Inc. Ocular implant delivery device and method
US10363255B2 (en) 2014-08-08 2019-07-30 Forsight Vision4, Inc. Stable and soluble formulations of receptor tyrosine kinase inhibitors, and methods of preparation thereof
US9474756B2 (en) 2014-08-08 2016-10-25 Forsight Vision4, Inc. Stable and soluble formulations of receptor tyrosine kinase inhibitors, and methods of preparation thereof
US10765677B2 (en) 2014-08-08 2020-09-08 Forsight Vision4, Inc. Stable and soluble formulations of receptor tyrosine kinase inhibitors, and methods of preparation thereof
US9895369B2 (en) 2014-08-08 2018-02-20 Forsight Vision4, Inc Stable and soluble formulations of receptor tyrosine kinase inhibitors, and methods of preparation thereof
US11617644B2 (en) 2014-10-13 2023-04-04 W. L. Gore & Associates, Inc. Prosthetic valved conduit
US11110001B2 (en) 2014-11-10 2021-09-07 Forsight Vision4, Inc. Expandable drug delivery devices and methods of use
US10500091B2 (en) 2014-11-10 2019-12-10 Forsight Vision4, Inc. Expandable drug delivery devices and methods of use
US11224602B2 (en) 2015-04-13 2022-01-18 Forsight Vision5, Inc. Ocular insert composition of a semi-crystalline or crystalline pharmaceutically active agent
US10010502B2 (en) 2015-05-19 2018-07-03 Amorphex Therapeutics Llc Device that delivers a sustained low-dose of a myopia-suppressing drug, while preserving pupillary function and accommodation
US10172740B2 (en) 2015-11-06 2019-01-08 David E Freilich Lacrimal stent
US11432959B2 (en) 2015-11-20 2022-09-06 Forsight Vision4, Inc. Porous structures for extended release drug delivery devices
US11617680B2 (en) 2016-04-05 2023-04-04 Forsight Vision4, Inc. Implantable ocular drug delivery devices
WO2018119188A2 (en) 2016-12-21 2018-06-28 Johnson & Johnson Vision Care, Inc. Extended period timer circuits for ophthalmic devices
US11351058B2 (en) 2017-03-17 2022-06-07 W. L. Gore & Associates, Inc. Glaucoma treatment systems and methods
US11523940B2 (en) 2017-03-17 2022-12-13 W. L. Gore & Associates, Inc. Delivery aids for glaucoma shunts
US11406533B2 (en) 2017-03-17 2022-08-09 W. L. Gore & Associates, Inc. Integrated aqueous shunt for glaucoma treatment
US11419759B2 (en) 2017-11-21 2022-08-23 Forsight Vision4, Inc. Fluid exchange apparatus for expandable port delivery system and methods of use
US11678983B2 (en) 2018-12-12 2023-06-20 W. L. Gore & Associates, Inc. Implantable component with socket

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