Abstract: A drug delivery device for placement in the eye includes a drug core comprising a pharmaceutically active agent, and a holder that holds the drug core. The holder is made of a material impermeable to passage of the active agent and includes an opening for passage of the pharmaceutically agent therethrough to eye tissue. The device includes a layer of material permeable to passage of the active agent. In assembling the device, a pin or weight, having a shape similar to the drug core, is used during curing of the permeable material.

Abstract: A treatment for dry eye and other eye problems using a plug system or a delivery system. The plug system comprises solid, porous or hollow microcapsules composed of a biodegradable biocompatible polymer. The capsules are stored in the form of a powder that can be suspended in an aqueous carrier solution or dispersed in a gel or an ointment. Alternatively a biodegradable biocompatible capsule having a treating agent encapsulated within a polymer shell or a polymer sphere, again stored in the form of a powder that can be suspended in an aqueous carrier solution or dispersed in a gel or an ointment. The plug system prevents excretion of the capsules and their size is larger then the punctum and to prevent entrance to the lachrymal excretory system. The treatment is slowly released into the eye through the polymer shell or sphere and/or gets secreted as the polymer degrades.

Abstract: A surgically implantable and sealable delivery device that upon contact of its contents via an interface window or port therein with an organ or tissue exposes a therapeutic agent to the organ or tissue surface, allowing a controlled, selective and unidirectional diffusion of the agent into the tissue or organ. The device protects adjacent organs or tissue structures from unnecessary high levels of the delivered agent. Novel methods to deliver chemotherapeutics or bioactive agents to mammalian organs or tissues through a surgically implanted device by the way of a selective and protected diffusion mechanism are disclosed as well as method to achieve the sealing properties of the device.

Abstract: This invention relates to formulations for the prevention of infection and/or abnormal conditions of mucosae and/or skin caused by any pathogen and/or any disease, and more particularly for the prevention of sexually transmitted infections specially HIV and HSV. This invention also relates to formulations for the treatment of infection and/or abnormal conditions of skin and/or mucosac and more particularly for the treatment of herpetic lesions. The formulations could be used as a prophylactic agent to prevent accidental infection of health care workers. The formulations could be used for the healing and/or treatment of bum wounds and prevention of further infection. This invention also relates to the development of a unique vaginal/ano-rectal applicator for the uniform delivery of any topical formulations to treat and/or prevent any infection and/or abnormal conditions of mucosa cavity caused by any pathogen and/or disease.

Abstract: An implant device is provided which incorporates a retinoid for improving the biocompatibility of the device in tissue. The device may be bioerodible for the purpose of systemically or locally releasing a therapeutic agent in tissue or it may be a permanent implant which includes a surface treated with a retinoid for increasing the biocompatibility thereof.

Abstract: The present invention features hydrogel drug delivery systems and methods of producing and using such systems for the treatment of wounds. The systems are based on a hydrogel into which a low concentration of growth factor, e.g., epidermal growth factor, is passively transferred from a dilute aqueous solution. When placed in contact with a wounded tissue, the growth factor passively transfers out of the contact lens to provide accelerated healing. The systems are applicable to ocular and other wound treatments.

Abstract: The present invention is directed to ophthalmic compositions containing a gelling amount of a combination of galactomannan polysaccharides and borates. The compositions gel or partially gel upon administration to the eye. The present invention also discloses methods of topical ophthalmic administration of the compositions to the eye.

Abstract: Devices and methods are provided for administering a fluid to a neuronal site. The device comprises a reservoir, an aperture in fluid connection to the reservoir, and electrical means for moving to the fluid to or through the aperture. The electrical means may take the form of electroosmotic force, piezoelectric movement of a diaphragm or electrolysis of a solution. The electrical means may be external to the host, implanted in the host or may be photodiodes activated by light, particularly where the neuronal site is associated with the retina.

Abstract: Methods of producing an intraocular lens include introducing a solution into a lens forming enclosure, wherein the solution comprises discrete crosslinkable units of a size small enough to provide an optically clear solution while contributing to a high refractive index of at least 1.3, performing crosslinking between the units of the solution, and thereby forming a solid lens in the enclosure, optionally under a forming pressure.

Abstract: Bioadhesive, closed-cell foam film, sustained release, delivery devices for administering an active agent or combination of active agents to a subject are provided. Methods for making such delivery devices and methods for using such delivery devices offering the controlled and sustained release of an active agent or combination of active agents to a subject, preferably a near zero-order release, are also provided.

Abstract: A method for repairing a retinal system of an eye, using bucky paper on which a plurality of retina pigment epithelial cells and/or iris pigment epithelial cells and/or stem cells is deposited, either randomly or in a selected cell pattern. The cell-covered bucky paper is positioned in a sub-retinal space to transfer cells to this space and thereby restore the retina to its normal functioning, where retinal damage or degeneration, such as macular degeneration, has occurred.

Abstract: The present invention are directed to P1, P4-di(uridine 5?-)tetraphosphate, tetra-alkali metal salts such as tetrasodium, tetralithium, tetrapotassium, and mixed tetra-alkali metal cations thereof. The tetra alkali metal salts of P1, P4-di(uridine 5?-)tetraphosphate are water-soluble, nontoxic, and easy to handle during manufacture. These tetra-monovalent alkali metal salts are more resistant to hydrolysis than the mono-, di-, or tri-acid salts, therefore, they provide an improved stability and a longer shelf life for storage. The present invention also provides methods for the synthesis of P1, P4-di(uridine 5?-)tetraphosphate, and its pharmaceutically acceptably acceptable salts thereof, and demonstrates the applicability to the production of large quantities. The methods substantially reduce the time required to synthesize diuridine tetraphosphate, for example, to three days or less.

Abstract: There is provided a pharmaceutical composition suitable for topical administration to an eye, the composition comprising (a) a pharmacologically effective concentration of an active agent and (b) a combination of at least two ophthalmically compatible polymers comprising a novel gum system. In preferred embodiments of the present invention, the compositions increase the retention time of the active agent in the eye, when compared to compositions with other gums or gum systems.

Abstract: An eyelid implant for implanting in an upper eyelid of a person having a main body with a water-drop shape. The main body has a head end with a center of gravity at substantially a center point thereof, and a tail end. The diameter of the head end is greater than a diameter of the tail end. At least one suture hole extends completely through the main body. At least one suture channel extends partially through the main body to a predetermined depth. A suture is passed through the at least one suture hole for securing the eyelid implant to an eyelid of a user and said implant causes said eyelid to close.

Abstract: The present invention is related to glucose sensors that are capable of detecting the concentration or level of glucose in a solution or fluid having either low or high ionic strength. The glucose sensors of the present invention comprise a polymerized crystalline colloidal array (PCCA) and a molecular recognition component capable of responding to glucose. The molecular recognition component may be a boronic acid, such as a phenylboronic acid, glucose oxidase, a combination of phenylboronic acid and poly(ethylene)glycol or crown ether, or another component capable of detecting glucose in various fluids and solutions. The glucose sensors of the present invention may be useful in the development of noninvasive or minimally invasive in vivo glucose sensors for patients having diabetes mellitus.

Abstract: Containing at least one macrolide antibiotic and/or mycophenolic acid provide anti-inflammatory, anti-cell proliferation, anti-cell migration, anti-angiogenesis, antimicrobial, and antifungal effects. In one embodiment, the solution is administered intraocularly after cataract surgery before insertion of a replacement intraocular lens, resulting in reduced posterior capsular opacification which may eliminate the need for a subsequent surgery. The solution may be one that is invasively administered, for example, an irrigation or volume replacement solution containing at least one macrolide antibiotic such as tacrolimus, sirolimus, everolimus, cyclosporine, and ascomycin, or mycophenolic acid. The solution may be one that is non-invasively or topically administered in the form of drops, ointments, gels, creams, etc. and may include eye lubricants and contact lens solutions.

Abstract: A method for improving the integrity of the corneal epithelium by introducing into the eye an effective amount of a ophthalmically compatible retinoid sufficient to enhance the integrity of the corneal epithelium.

Abstract: A formulation to treat ocular conditions such as dry eye disease, as well as other conditions, is disclosed. Rapamycin and/or ascomycin is administered intraocularly, such as by topical application, injection into the eye, or implantation in or on the eye. For example, a topical administration may contain between about 50 pg/ml drug to about 50 ?g/ml drug in a formulation which may be applied at bedtime or throughout the day. For injection, a dose of about 50 pg/ml to about 200 ?g/ml may be used. Rapamycin and/or ascomycin may also be administered in milligram quantities as a surgical implant, for example, in a diffusible walled reservoir sutured to the wall of the sclera, or may be contained within an inert carrier such as microspheres or liposomes to provide a slow-release drug delivery system.

Abstract: Ocular solutions containing at least one macrolide antibiotic and/or mycophenolic acid provide anti-inflammatory, anti-cell proliferation, anti-cell migration, anti-angiogenesis, antimicrobial and antifungal effects. In one embodiment, the solution is administered intraocularly after cataract surgery before insertion of a replacement intraocular lens, resulting in reduced posterior capsular opacification which may eliminate the need for a subsequent surgery. The solution may be one that is invasively administered, for example, an irrigation or volume replacement solution containing at least one macrolide antibiotic such as tacrolimus, sirolimus, everolimus, cyclosporine, and ascomycin, or mycophenolic acid. The solution may be one that is non-invasively or topically administered in the form of drops, ointments, gels, creams, etc. and may include eye lubricants and contact lens solutions.

Abstract: The present invention provides a method of treating edematous retinal disorders. The method comprises administration of a pharmaceutical formulation comprising a hydrolysis-resistant P2Y receptor agonist to stimulate the removal of pathological extraneous fluid from the subretinal and retinal spaces and thereby reduce the accumulation of said fluid associated with retinal detachment and retinal edema. The P2Y receptor agonist can be administered with therapeutic and adjuvant agents commonly used to treat edematous retinal disorders. The pharmaceutical formulation useful in this invention comprises a P2Y receptor agonist with enhanced resistance to extracellular hydrolysis, such as dinucleoside polyphosphate compounds, or hydrolysis-resistant mononucleoside triphosphates.

Abstract: An intraocular lens suitable for implantation into an eye has an optically clear, deformable lens body composed of a silicone polymer and a silica reinforcer that structurally reinforces the polymer. The silica reinforcer is chemically modified with aryl groups effective to increase the refractive index of the silica reinforcer, preferably so as to substantially match the refractive index of the silicone polymer.

Abstract: The present invention is concerned with biomedical device comprising (a) a biocompatible organic or inorganic bulk material and (b) a coating comprising polymerizable carbon-carbon double bonds covalently attached to at least part of the bulk surface. The biomedical devices of the invention are radiation sensitive and may be used, for example, as ready-to-use corneal onlay in ophthalmic surgery.

Abstract: Azalide antibiotics such as azithromycin are useful in the treatment and prevention of infections by bacteria and other parasites. Stabilized aqueous compositions containing azithromycin suitable for administration without reconstitution are provided for. Also provided for are aqueous formulations suitable for ocular administration in a employing a convenient dosing formulation suitable for administration in depot formats.

Abstract: The present invention encompasses a solid dose delivery vehicle for ballistic administration of a bioactive material to subcutaneous and intradermal tissue, the delivery vehicle being sized and shaped for penetrating the epidermis. The delivery vehicle further comprises a stabilizing polyol glass loaded with the bioactive material and capable of releasing the bioactive material in situ. The present invention further includes methods of making and using the solid dose delivery vehicle of the invention.

Abstract: The invention concerns a semipermeable chamber for encapsulation of cells producing at least a biological substance of interest, characterised in that it consists of a porous polycarbonate biocompatible film modified at the surface by generated polar sites and covered with at least a layer of hydrophilic polymer.

Abstract: The present invention is directed to a coated biomedical device said micelle having a hydrophilic outer shell and a hydrophobic inner core, or a hydrophobic outer shell and a hydrophilic inner core said micelle comprised of a block copolymer having a HLB value ranging from about 1 to about 40. The medical device may have one coating thereon or multiple coatings. The present invention is also directed to the use of the micelle as a drug carrier.

Abstract: A method for treating or preventing retinal pathology or injury. The method locates and secures a retinal stimulating substance in the eye between the internal limiting membrane and the retina, which is the target site for the substance. The substance may be an implant that provides electrical stimulation to adjacent ganglion and neurofiber cells. Alternatively, the substance may be a pharmaceutical substance to stimulate the retina. In addition to providing direct contact of the substance with its target, the method obviates the need for artificial structures such as tacks or adhesives which may cause retinal bleeding or traction.

Abstract: The present invention provides a composition for topical administration comprising an interleukin 2 inhibitor and an antimicrobial agent as active ingredients thereof, wherein said interleukin 2 inhibitor contains a tricyclo compound as shown by the general formula (I) or pharmaceutically acceptable salt thereof. The present invention further provides a method for treating inflammations and/or infections comprising topical administration of an effective amount of an interleukin 2 inhibitor and an antimicrobial agent to a subject in need of the treatment of inflammations and/or infections.

Abstract: Disclosed are invasive and non-invasive central nervous system (CNS) drug delivery methods and devices for use in these methods that essentially circumvent the blood-brain barrier. More specifically, the disclosed methods and devices utilize iontophoresis as delivery technique that allows for enhanced delivery of a biologically active agent into the CNS of a mammal as well as for (pre)-programmable and controlled transport.

Abstract: Methods for reducing or preventing transplant rejection in the eye of an individual are described, comprising: a) performing an ocular transplant procedure; and b) implanting in the eye a bioerodible drug delivery system comprising an immunosuppressive agent and a bioerodible polymer.

Abstract: There are provided lubricious ophthalmic solutions having a pH of between about 7.0 and about 8.0, consisting essentially of an aqueous solution of from about 0.5–4% by weight of a monographed polyol, borate calculated as the borate equivalent of 20–100% by weight of boric acid relative to said polyol, from about 0.1 to about 1.00% by weight of monographed polysorbate, a monographed preservative and a buffer. Suitably the polyol is polyvinyl alcohol In addition to polyvinyl alcohol (hereinafter PVA) the solution may include other monographed polymers as well as monographed pharmacologically active substances.

Abstract: A flat strip of supporting material, such as filter paper, having marked reference locations on each of one or more legs, for delivering controlled quantities of one or more agents to the adnexa of the eye simultaneously upon dispensing a liquid to the strip at the appropriate reference location.

Abstract: The invention provides microfabricated devices and methods for directing the growth of a cell process to form an artificial synapse. The devices are called artificial synapse chips. The artificial synapse comprises a nanofabricated aperture (about 50–100 nm in size) that connects the cell process to a chemical or electrical means of neuronal excitation. Such an aperture width mimics the length scales of a natural synapse and thus emphasizes the localized spatial relationship between a neuron and a stimulation source. The invention further provides devices and methods for regenerating a nerve fiber into an electrode. The invention thus provides a regeneration electrode that uses a novel neural interface for stimulation and that uses novel surface methods for directing neuronal growth making possible in vivo connection of the devices to neural circuitry in a retina and other anatomical locations.

Abstract: A tear replacement solution that contains at least one water-soluble fluorosurfactant, water and a non-polar component, preferably in gel form, and a method for the external treatment for the eye of an mammal by applying the tear replacement solution to the eye, preferably by placing in the conjunctival sac.

Abstract: Disclosed is an improved sustained release drug delivery device and method of producing such device. The device comprises a drug core in an impermeable cup or impermeable coating layer that is adhered to an uncured suture tab and covered with a permeable polymer coating layer that is similar to the makeup of the suture tab. The permeable polymer coating layer that covers the device, covering the impermeable coating layer and at least a portion of the drug core, is cured (after drying) along with the uncured suture tab. The “cocuring” or one step curing process forms a very strong bond between the outer coating layer to the suture tab preventing leaks.

Abstract: An ophthalmic drug delivery device having a scleral surface, an orbital surface, an injection port on the orbital surface, and a fluid conducting passageway disposed within the device that is fluidily coupled to the injection port and terminates in an opening for communicating the fluid to an outer surface of the sclera is disclosed. The fluid contains a pharmaceutically active agent useful for the treatment of a disease of the posterior segment of the eye.

Abstract: An improved punctum plug is more easily visualized when positioned within a punctual canal of a recipient. The body of the plug features an outwardly exposed surface when properly positioned, and a substance causing at least the outwardly exposed surface to contrast with surrounding tissue, such that the use of the substance causes the plug to be more easily visualized than if the substance were not present. The substance, which may be disposed on the outwardly exposed surface or within the body of the plug, may include a saturated coloration, or may be phosphorescent, fluorescent or otherwise operative to reflect or re-radiate light to assist in visualization. For example, the substance may include an organic or inorganic phosphor or fluorescent material, reflective beads, quantum dots, a dye or pigment. Such reflection or re-radiation may occur at the same or different wavelength(s) compared to the illumination wavelength(s), whether or not either or both are within the visible part of the spectrum.

Abstract: Methods for treating neurological or neuropsychiatric diseases or disorders in humans by administering to the human a therapeutically effective dose of specific biologics are presented. The biologics of consideration include antagonists of tumor necrosis factor or of interleukin-1. The administration of these biologics is performed by specific methods, most, but not all of which fall into the category of anatomically localized administration designed for perispinal use. Anatomically localized administration involving perispinal use includes, but is not limited to the subcutaneous, intramuscular, interspinous, epidural, peridural, parenteral or intrathecal routes. Additonally, intranasal administration is discussed as a method to provide therapeutic benefit.

Abstract: Methods for preparing products containing moisture-sensitive materials, including biological materials such as proteins, peptides or live cells, comprising at least the steps: (i) providing a coating liquid comprising at least one active, a sugar polymer and a water soluble/miscible solvent; (ii) providing a quantity of microparticles comprising at least water soluble gel forming solid particles; (iii) fluidizing said quantity of microparticles within a processing chamber of a of a suitable apparatus to form a fluidized bed of said microparticles; (iv) spraying said coating liquid onto said fluidized bed from beneath the fluidized bed to coat said microparticles therewith under saturated moisture conditions; and (vi) allowing coated microparticles to dry, are described. Also described are compositions and uses.

Abstract: The present invention is directed to an improved sustained release drug delivery device comprising a drug core, a unitary cup, and a prefabricated permeable plug.

Abstract: The invention is directed to a composite material, especially a biomedical device, e.g. an ophthalmic device, preferably a contact lens, with one or more wettable surfaces capable of holding a continuous layer of aqueous fluid thereon which composite material comprises a bulk material and a hydrophilic coating characterized in that the hydrophilic coating consists of a carbohydrate attached covalently to reactive groups at the surface of the bulk material, either directly or via functional groups of an oligofunctional compound, said oligofunctional compound in turn having functional groups being capable of reacting with said reactive groups at the surface of the bulk material and with the carbohydrate, wherein said reactive groups are either inherently (a priori) present in the bulk material or wherein said reactive groups have been attached to the surface of the bulk material by a plasma surface preparation, as well as to a process of manufacture of such a composite material.

Abstract: The present invention provides solid pharmaceutical compositions for improved delivery of a wide variety of pharmaceutical active ingredients contained therein or separately administered. In one embodiment, the solid pharmaceutical composition includes a solid carrier, the solid carrier including a substrate and an encapsulation coat on the substrate. The encapsulation coat can include different combinations of pharmaceutical active ingredients, hydrophilic surfactant, lipophilic surfactants and triglycerides. In another embodiment, the solid pharmaceutical composition includes a solid carrier, the solid carrier being formed of different combinations of pharmaceutical active ingredients, hydrophilic surfactants, lipophilic surfactants and triglycerides. The compositions of the present invention can be used for improved delivery of hydrophilic or hydrophobic pharmaceutical active ingredients, such as drugs, nutritional agents, cosmeceuticals and diagnostic agents.

Abstract: This invention provides: 1) a method of treating androgen-deprivation induced osteoporosis and/or bone fractures and/or loss of Bone Mineral Density (BMD) in a male subject suffering from prostate cancer; 2) a method of preventing androgen-deprivation induced osteoporosis and/or bone fractures and/or loss of Bone Mineral Density (BMD) in a male subject suffering from prostate cancer; 3) a method of suppressing or inhibiting androgen-deprivation induced osteoporosis and/or bone fractures and/or loss of BMD in a male subject suffering from prostate cancer; and 4) a method of reducing the risk of developing androgen-deprivation induced osteoporosis and/or bone fractures and/or loss of BMD in a male subject suffering from prostate cancer, by administering to the subject a pharmaceutical composition comprising an anti-estrogen agent and/or its analog, derivative, isomer, metabolite, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof as described herein.

Abstract: The present invention encompasses a solid dose delivery vehicle for ballistic administration of a bioactive material to subcutaneous and intradermal tissue, the delivery vehicle being sized and shaped for penetrating the epidermis. The delivery vehicle further comprises a stabilizing polyol glass loaded with the bioactive material and capable of releasing the bioactive material in situ. The present invention further includes methods of making and using the solid dose delivery vehicle of the invention.

Abstract: The present invention is directed to a method of treating pain. The method comprises administering to a subject a pharmaceutical composition comprising an effective amount of a P2X receptor antagonist. The methods of the present invention are useful in reducing pain, such as traumatic pain, neuropathic pain, organ pain and pain associated with diseases. The P2X receptor antagonists particularly useful for this invention are mononucleoside polyphosphate derivatives or dinucleoside polyphosphate derivatives of general Formula I. The compounds of the present method can be used alone to treat pain. The compounds of the present method can also be used in conjunction with other therapeutic agents or adjunctive therapies commonly used to treat pain, thus enhancing the overall pain-reducing effect in a subject in need of such treatment.

Abstract: The present invention is directed to P1, P4-di(uridine 5?)-tetraphosphate, tetra-alkali metal salts such as tetrasodium, tetralithium, tetrapotassium, and mixed tetra-alkali metal cations thereof. The tetra alkali metal salts of P1, P4-di(uridine 5?)-tetraphosphate are water-soluble, nontoxic, and easy to handle during manufacture. These tetra-monovalent alkali metal salts are more resistant to hydrolysis than the mono-, di-, or tri-acid salts, therefore, they provide an improved stability and a longer shelf life for storage. The present invention also provides methods for the synthesis of P1, P4-di(uridine 5?)-tetraphosphate, and its pharmaceutically acceptably acceptable salts thereof, and demonstrates the applicability to the production of large quantities. The methods substantially reduce the time required to synthesize diuridine tetraphosphate, for example, to three days or less.

Abstract: The present invention provides a method of reducing intraocular fibrin comprising the administration of a pharmacologically effective dose of Protein C to an individual having elevated levels of intraocular fibrin. Also provided are various methods of preventing intraocular fibrin formation, treating intraocular diseases and reducing intraocular inflammation.

Abstract: Methods of producing an intraocular lens in vivo comprise preparing a composition of discrete water soluble macromolecular particles, mixing the composition with a water soluble photoinitiator and forming an opthalmically acceptable aqueous solution having a refractive index of at least 1.39, injecting the resulting aqueous solution into the capsular bag of an eye, and initiating crosslinking between the macromolecular particles by irradiation of a wavelength in the range of about 380 to 700 nm to create a lens in the capsular bag.

Abstract: Personal care and hygiene formulations for topical application to mucosal surfaces. These formulations include an amphiphilic lipid carrier in the form of a colloidal composition which can include a micellar aggregate or mixed micelles dispersed in a continuous aqueous phase, or an emulsion of lipid droplets suspended in a continuous aqueous phase, and an active agent which is an anti-microbial agent. The lipid carrier has high adhesiveness to mucous membranes such as the soft tissues of the oral cavity. The lipid carrier also has a high load capacity for the active agent to be carried to these tissues. These formulations have the desirable properties of carrying a large amount of active agent for controlled and prolonged release thereof at the desired site, such as mucous membrane surfaces and surrounding tissue. Accordingly, the present invention provides a formulation for oral or topical application including an anti-microbial agent and a lipid.

Abstract: A polyurethane based prepolymer is provided and useful in biomedical devices which provides high oxygen permeability and superior physical properties. A hydrogel is produced from a comonomer mixture containing a polysiloxane-containing urethane prepolymer, tris(trimethylsiloxy)-silylpropyl methacrylate and a hydrophilic comonomer. The hydrogel is especially useful for biomedical materials such as contact lenses and implants.