WO1995031968A1 - Non-steroidal anti-inflammatory ophthalmic suspensions - Google Patents
Non-steroidal anti-inflammatory ophthalmic suspensions Download PDFInfo
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- WO1995031968A1 WO1995031968A1 PCT/US1995/006192 US9506192W WO9531968A1 WO 1995031968 A1 WO1995031968 A1 WO 1995031968A1 US 9506192 W US9506192 W US 9506192W WO 9531968 A1 WO9531968 A1 WO 9531968A1
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- WIPO (PCT)
- Prior art keywords
- composition
- suspension
- diclofenac
- agent
- recited
- Prior art date
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/12—Ophthalmic agents for cataracts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Definitions
- the present invention relates to ophthalmic formulations and more particularly, ophthalmic formulations of non-steroidal anti-inflammatory agents, particularly diclofenac sodium.
- Cyclooxygenase is essential in the biosynthesis of prostaglandins which have been shown in many animal models to be mediators of intraocular inflammation. Although sterioidal compounds have been used to treat such inflammation, non-steroidal anti-inflammatory agents, from the group of drugs
- cyclooxygenase inhibitors have been substituted for steroids because they have not shown the same propensity to produce side-effects in ocular tissues as ophthalmic steroids.
- Non-steroidal agents are also widely prescribed to reduce pain and inflammation in a wide number of tissues. When used as topical agents in the eye, they suppress inflammatory responses and to prevent particular side-
- Diclofenac sodium, suprofen, and flurbiprofin are non-steroidal anti- inflammatory agents that have been used for the treatment of postoperative inflammation in patients who have undergone cataract extraction.
- Anti-inflammatory agents have in the past been administered in solutions at neutral pH. Injection of anti-inflammatory agents in the form of a
- U.S. Patent No. 4,829,083 to Doulakas relates to stabilization of mercury-containing preservatives in liquid or gel ophthalmic medicaments with addition of 2-amino-2-hydroxymethyl-l, 3-propanediol or a homologue thereof.
- U.S. Patent No. 4,829,088 to Doulakas also relates to an ophthalmic medicament containing diclofenac sodium in aqueous solution.
- the solution contains 2-amino-2-hydroxymethyl-l, 3-propanediol as a preservative.
- U.S. Patent No. 5, 110,493 to Cherng-Chyi et al. relates to ophthalmic non-steroidal anti-inflammatory drug formulations containing a quaternary ammonium preservative and a non-ionic surfactant.
- non-steroidal anti-inflammatory agents when used in a topical solution, however, sting upon placement in the eye.
- the transient burning and stinging causes tearing, which in turn, washes the drug away from the eye, resulting in reduced bioavailability of the drug.
- the conventional solutions of non-steroidal anti-inflammatory agents generally have a pH of 7.0 to about 8.0. This pH level provides complete solubility of the drug, thereby allowing for a high concentration of the drug to be immediately available to the cornea.
- the high concentration of the drug on the eye aggravates the burning and stinging effects of the drug.
- the present invention provides topical ophthalmic formulations containing non-steroidal anti-inflammatory agents which reduce or eliminate the stinging and burning experienced with solutions of anti-inflammatory agents.
- Formulations of the present invention may be useful for treatment of any condition that may be treated by a non-steroidal anti-inflammatory agent.
- One embodiment of the present invention is a topical ophthalmic composition for treatment of the eye comprising an aqueous suspension of a non- steroidal anti-inflammatory agent, the composition having a pH and concentration of agent chosen to ensure that at least some of the agent is in suspension.
- the present invention also provides a method for treating diseases of the eye, including inflammation, by topically applying such suspensions to eyes in need of treatment.
- the present invention provides a composition for treating the eye topically comprising an aqueous mixture of a non-steroidal anti-inflammatory agent, wherein the composition has a pH of about 4.0 to about 8.0, preferably about 5.0 to about 6.8, and at least some of the agent is maintained as a reservoir established in suspension at the pH of the formulation.
- the amount established in suspension may vary depending on therapeutic needs but it will be at least an amount sufficient to have a therapeutic effect on the eye upon delayed release from the suspension over a period of time. A sufficient amount of agent will also be present in solution to have an immediate therapeutic effect upon topical ophthalmic application.
- the total agent contained in the mixture will be in suspension, but this may vary depending on how much of the agent is desired for delivery and the duration of delivery desired.
- the amount of therapeutic agent in suspension may, for instance, range from about 70% to about 99% or about 10% to about 99% by weight of the total amount of agent contained in the mixture.
- the compositions will not, however, have 100% of the agent in suspension. Some amount will be in solution to provide the immediate therapeutic effect.
- compositions of the present invention may have a pH of about 4 to about 8 depending on the solubility characteristics of the agent.
- a preferred pH range is about 5.0 to about 6.8.
- the concentration of the agent and the pH of the composition will be selected to ensure that a sufficient amount of the therapeutic agent is in suspension to provide a therapeutic effect upon delayed delivery. In this way, the portion of the agent in solution is immediately available for therapeutic effect while the portion in suspension serves as a reservoir and is released slowly over time.
- the solubility of non-steroidal anti-inflammatory agents is pH dependent, i.e., normally the higher the pH, the higher the solubility of the drug in the formulation.
- a formulation containing 1% diclofenac sodium has virtually all of the diclofenac in suspension.
- Formulating the composition as a suspension rather than as a solution inhibits immediate contact between the drug and tissues of the eye and in that way reduces the stinging and burning sensation experienced when a solution of such drugs places all of the drug in immediate contact with the ocular tissues.
- non-steroidal anti-inflammatory drugs have different solubilities at a given pH. These differences in solubility are known or can be ascertained with techniques familiar to those of ordinary skill in the art.
- the amount of non-steroidal anti-inflammatory agent in suspension for use in the present compositions will therefore vary depending, for example, on the specific agent or drug chosen, the dosage required, the desired release profile (the degree of sustained release), the condition for which the drug is administered and the pH of the composition. Generally, however, it is preferred to have formulations with about 70% - 99% of the total NSAI in suspension although other amounts may be used (such as 10% - 99%), so long as at least some of the agent is in suspension; that is an amount sufficient to have a therapeutic effect during delayed release.
- a therapeutic amount must also be in solution.
- the total amount of therapeutic agent, or drug is present in the composition in an amount effective to treat the selected target condition.
- the concentration will generally be about 0.001 to about 5.0% by weight of the composition.
- the drug is about 0.005 to about 3.0% by weight of the composition, and more preferably about 0.1 to about 1.0% by weight of said composition.
- Non-steroidal anti-inflammatory agents as used herein are intended to mean any non-narcotic analgesic/non-steroidal anti-inflammatory compound useful as a cyclooxygenase inhibitor.
- the non-steroidal anti- inflammatory agent is one or more of the following: aspirin, benoxaprofen, benzofenac, bucloxic acid, butibufen, carprofen, cicloprofen, cinmetacin, clidanac, clopirac, diclofenac, etodolac, fenbufen, fenclofenac, fenclorac, fenoprofen, fentiazac, flunoxaprofen, furaprofen, flurbiprofen, furobufen, furofenac, ibuprofen, ibufenac, indomethacin, indoprofen, isoxepac, ketroprofen, lactorolac
- the pH and concentration of the agent in the formulation are selected to provide sufficient drug in solution to begin effective therapeutic treatment but at least some in suspension to serve as a depot for the agent which delays release of that agent over time.
- the pH of the aqueous mixture may be about 4.0 to about 8.0 and preferably, about 5.0 to about 6.8, but at a level sufficient to establish the desired suspension amount of non-steroidal anti- inflammatory agent.
- the composition may be formulated as an aqueous suspension.
- the composition may contain water soluble polymers or water insoluble polymers as the suspending agent. Examples of such soluble polymers are cellulosic polymers like hydroxypropyl methylcellulose. Water insoluble polymers are preferably crosslinked carboxy-vinyl polymers. It is important to note, however, that the present invention requires the drug to be in suspension without reference to whether the polymer is or is not in suspension. A preferred form of the invention incorporates insoluble polymers to provide a gel or liquid drops which release the drug over time.
- the polymer is about 0.1 to about 6.5%, more preferably about 1.0 to about 1.3% by weight based on the total weight of the suspension of a crosslinked carboxy- containing polymer.
- Suitable carboxy-containing polymers for use in the present invention and method for making them are described in U.S. Patent No. 5,192,535 to Davis et al. which is hereby incorporated by reference and relied upon.
- These polymer carriers include lightly crosslinked carboxy-containing polymers (such as polycarbophil, or Carbopols®), dextran, cellulose derivatives, polyethylene glycol 400 and other polymeric demulcents such as polyvinylpyrolidone, polysaccaride gels and Gelrite®.
- a carboxy-containing polymer system known by the tradename DuraSite®, containing polycarbophil is a sustained release topical ophthalmic delivery system that releases the drug at a controlled rate, may also be used.
- Aqueous mixtures of this invention may also contain amounts of suspended lightly crosslinked polymer particles ranging from about 0.1% to about 6.5% by weight, and preferably from about 0.5% to about 4.5% by weight, based on the total weight of the aqueous suspension.
- They will preferably be prepared using pure, sterile water, preferably deionized or distilled, having no physiologically or ophthalmologically harmful constituents, and will be adjusted to a pH of from about 4.0 to about 6.8, and preferably from about 5.5 to about 6.5, using any physiologically and ophthalmologically acceptable pH adjusting acids, bases or buffers, e.g., acids such as acetic, boric, citric, lactic, phosphoric, hydrochloric, or the like, bases such as sodium hydroxide, sodium phosphate, sodium borate, sodium citrate, sodium acetate, sodium lactate, THAM (trishydroxymethylamino-methane), or the like and salts and buffers such as citrate /dextrose, sodium bi
- ⁇ When formulating the aqueous suspensions, their osmotic pressure ( ⁇ ) may be adjusted to from about 10 milliosmolar (mOsM) to about 400 mOsM, using appropriate amounts of physiologically and ophthalmologically acceptable salts.
- mOsM milliosmolar
- Sodium chloride is preferred to approximate physiologic fluid, and amounts of sodium chloride ranging from about 0.01% to about 1% by weight, and preferably from about 0.05% to about 0.45% by weight, based on the total weight of the aqueous suspension, will give osmolalities within the above-stated ranges.
- Equivalent amounts of one or more salts made up of cations such as potassium, ammonium and the like and anions such as chloride, citrate, ascorbate, borate, phosphate, bicarbonate, sulfate, thiosulfate, bisulfate, sodium bisulfate, ammonium sulfate, and the like can also be used in addition to or instead of sodium chloride to achieve osmolalities within the above-stated ranges.
- Sugars like mannitol, dextrose, glucose or other polyols may be added to adjust osmolarity.
- insoluble lightly crosslinked polymer particles, the pH, and the osmotic pressure chosen from within the above-stated ranges will be correlated with each other and with the degree of crosslinking to give aqueous suspensions having viscosities ranging from about 500 to about 100,000 centipoise, and preferably from about 5,000 to about 30,000 or about 5,000 to about 20,000 centipoise, as measured at room temperature (about 25 °C) using a Brookfield Digital LVT Viscometer equipped with a number 25 spindle and a 13R small sample adapter at 12 rpm.
- the viscosity will typically be about 10 to about 400 centipoises, more typically about 10 to about 200 centipoises or about 10 to about 25 centipoises.
- composition of the present invention will ordinarily contain surfactants and, if desired, adjuvants, including additional medicaments, buffers, antioxidants, tonicity adjusters, preservatives, thickeners or viscosity modifiers, and the like.
- Additives in the formulation may desirably include sodium chloride, EDTA (disodium edetate), and/or BAK (benzalkonium chloride) or sorbic acid.
- Non-steroidal anti-inflammatory agents are non-steroidal substances used in treating or ameliorating a disease or medical condition. They include drugs intended to treat therapeutically conditions of the eye itself or the tissue surrounding the eye and drugs administered via the ophthalmic route to treat therapeutically a local condition other than that involving the eye.
- the ophthalmic medicaments will typically be incorporated in the topical delivery systems of this invention in therapeutically active amounts comparable to amounts administered in other dosage forms, usually in amounts ranging from about 0.001% to about 5% by weight, and preferably from about 0.1% to about 1% by weight, based on the total weight of the formulation. Thus, for example, about 0.1% to about 1.0% by weight of the anti-inflammatory non-steroidal compound can be administered to the eye in this manner.
- the viscous gels that result from fluid eyedrops delivered by means of the aqueous suspensions of this invention typically have residence times in the eye ranging from about 2 to about 12 hours, e.g., from about 3 to about 6 hours.
- the agents contained in these drug delivery systems will be released from the gels at rates that depend on such factors as the drug itself and its physical form, the extent of drug loading and the pH of the system, as well as on any drug delivery adjuvants, such as ion exchange resins compatible with the ocular surface, which may also be present.
- the aqueous suspensions provide sustained concentration of the non-steroidal anti-inflammatory agent of between 10 ⁇ 8 " and 10 ⁇ 4 M, and more preferably between 10" ⁇ and 10 "5 M, in the aqueous or treated tissue of the eye for at least two hours, preferably at least three hours.
- Ophthalmic suspensions of the present invention may be formulated so that they retain the same or substantially the same viscosity in the eye that they had prior to administration to the eye.
- ophthalmic suspensions of the present invention may be formulated so that there is increased gelation upon contact with tear fluid. For instance, when a formulation containing DuraSite® is administered to the eye at a lower pH, the DuraSite® system swells upon contact with tears. This gelation or increase in gelation leads to entrapment of the suspended drug particles, thereby extending the residence time of the composition in the eye. The drug is released slowly as the suspended particles dissolve over time as the solubility of the drug is higher in the tear fluid.
- compositions of this invention can be formulated in any other suitable manner.
- diclofenac sodium may be dissolved and added by sterile filtration to a preparation containing sodium chloride, hydroxypropyl methyl cellulose and surfactant. This mixture may then be adjusted to the appropriate pH by known techniques, for example by the addition of sodium hydroxide. Other methods will be apparent to one skilled in the art.
- ophthalmic formulations suitable for topical ophthalmic administration may be formulated and administered in accordance with techniques familiar to persons skilled in the art.
- the finished formulations are preferably stored in opaque or brown containers to protect them from light exposure, and under an inert atmosphere.
- These aqueous suspensions can be packaged in preservative- free, single-dose non-reclosable containers. This permits a single dose of the medicament to be delivered to the eye as a drop or ribbon, with the container then being discarded after use.
- Such containers eliminate the potential for preservative-related irritation and sensitization of the corneal epithelium, as has been observed to occur particularly from ophthalmic medicaments containing mercurial preservatives.
- aqueous suspensions of this invention can also be used, if desired, particularly since the relatively low viscosities of the aqueous suspensions of this invention permit constant, accurate dosages to be administered dropwise to the eye as many times each day as necessary.
- suitable preservatives are chlorobutanol, polyquat, benzalkonium chloride, cetyl bromide, sorbic acid and the like.
- compositions of Examples 1 and 2 will be about 10 up to about 200 centipoises, preferably about 10 to about 25 centipoises.
- Examples 3-4 Noveon AA-1 is slowly dispersed into a beaker containing approximately 1/3 of the final weight of water and stirred for 1.5 hrs. with an overhead stirrer.
- Noveon AA-1 is an acrylic acid polymer available from B.F. Goodrich.
- Edetate sodium (EDTA) and sodium chloride are then added to the polymer solution and stirred for 10 minutes after each addition.
- the polymer suspension is at a pH of about 3.0-3.5.
- the mixture is sterilized by autoclaving at
- Diclofenac sodium is dissolved separately in approximately 1/2 of the final weight of water, added to the polymer mixture by sterile filtration (0.22 ⁇ m filter) and stirred for 10 minutes.
- the mixture is adjusted to pH 6.0 with ION sodium hydroxide, brought to final weight with water and surfactant by sterile filtration and aseptically filled into unit-dose containers.
- Examples 5-6 Noveon AA-1 is slowly dispersed into a beaker containing approximately 1/3 of the final weight of water and stirred for 1.5 hrs. with an overhead stirrer.
- Noveon AA-1 is an acrylic acid polymer available from B.F. Goodrich.
- Edetate sodium (EDTA) is then added to the polymer suspension and stirred for 10 minutes.
- the polymer suspension is at a pH of about 3.0-3.5.
- the mixture is sterilized by autoclaving at 121 °C for 20 minutes.
- Dextrose is dissolved in 1/10 of the final weight of water and sterile filtered (0.22 ⁇ m filter) in to the polymer suspension and stirred for 10 minutes.
- Diclofenac sodium is dissolved separately in approximately 1/2 of the final weight of water, added to the polymer mixture by sterile filtration and stirred for 10 minutes.
- the mixture is adjusted to pH 6.0 with ION sodium hydroxide, brought to final weight with water and surfactant by sterile filtration and aseptically filled into unit-dose containers.
- Examples 7-8 Noveon AA-1 is slowly dispersed into a beaker containing approximately 1/3 of the final weight of water and stirred for 1.5 hrs. with an overhead stirrer.
- Noveon AA-1 is an acrylic acid polymer available from B.F. Goodrich.
- Edetate sodium (EDTA), o-phosphoric acid, and sodium borate are then added to the polymer suspension and stirred for 10 minutes after each addition.
- the polymer solution is at a pH of about 3.0-3.5.
- the mixture is sterilized by autoclaving at 121° for 20 minutes.
- Diclofenac sodium is dissolved separately in approximately 1/2 of the final weight of water, added to the polymer mixture by sterile filtration (0.22 ⁇ m filter) and stirred for 10 minutes.
- the mixture is adjusted to pH 6.0 with ION sodium hydroxide, brought to final weight with water and surfactant by sterile filtration and aseptically filled into unit-dose containers.
- Noveon AA-1 is slowly dispersed into a beaker containing approximately 1/3 of the final weight of water and stirred for 1.5 hrs. with an overhead stirrer.
- Noveon AA-1 is an acrylic acid polymer available from B.F. Goodrich.
- Edetate sodium (EDTA), sodium chloride and mannitol are then added to the polymer suspension and stirred for 10 minutes after each addition.
- the polymer solution is at a pH of about 3.0-3.5.
- the mixture is sterilized by autoclaving at 121° for 20 minutes.
- Diclofenac sodium is dissolved separately in approximately 1/2 of the final weight of water, added to the polymer mixture by sterile filtration (0.22 ⁇ m filter) and stirred for 10 minutes.
- the mixture is adjusted to pH 6.0 with ION sodium hydroxide, brought to final weight with water and surfactant by sterile filtration and aseptically filled into unit-dose containers.
- Examples 11-14 Noveon AA-1 is slowly dispersed into a beaker containing approximately 1/3 of the final weight of water and stirred for 1.5 hrs. with an overhead stirrer.
- Noveon AA-1 is an acrylic acid polymer available from B.F. Goodrich.
- Edetate sodium (EDTA), sodium chloride and mannitol are then added to the polymer suspension and stirred for 10 minutes after each addition.
- the polymer solution is at a pH of about 3.0-3.5.
- the mixture is sterilized by autoclaving at 121° for 20 minutes.
- Suprofen or Flurbiprofen sodium is dissolved separately in approximately 1/2 of the final weight of water and the pH is adjusted to 7-8 with sodium hydroxide and it is then added to the polymer mixture by sterile filtration (0.22 ⁇ m filter) and stirred for 10 minutes.
- the mixture is adjusted to pH 6.0 with ION sodium hydroxide, brought to final weight with water and surfactant by sterile filtration and aspectically filled into unit-dose containers.
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU25529/95A AU695699B2 (en) | 1994-05-24 | 1995-05-19 | Non-steroidal anti-inflammatory ophthalmic suspensions |
CA002189424A CA2189424C (en) | 1994-05-24 | 1995-05-19 | Non-steroidal anti-inflammatory ophthalmic suspensions |
JP53039895A JP4158203B2 (en) | 1994-05-24 | 1995-05-19 | Non-steroidal anti-inflammatory ophthalmic suspension |
EP95919867A EP0764018A1 (en) | 1994-05-24 | 1995-05-19 | Non-steroidal anti-inflammatory ophthalmic suspensions |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/248,500 | 1994-05-24 | ||
US08/248,500 US6309630B1 (en) | 1994-05-24 | 1994-05-24 | Non-steroidal anti-inflammatory ophthalmic suspensions |
Publications (1)
Publication Number | Publication Date |
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WO1995031968A1 true WO1995031968A1 (en) | 1995-11-30 |
Family
ID=22939418
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/US1995/006192 WO1995031968A1 (en) | 1994-05-24 | 1995-05-19 | Non-steroidal anti-inflammatory ophthalmic suspensions |
Country Status (6)
Country | Link |
---|---|
US (1) | US6309630B1 (en) |
EP (1) | EP0764018A1 (en) |
JP (1) | JP4158203B2 (en) |
AU (1) | AU695699B2 (en) |
CA (1) | CA2189424C (en) |
WO (1) | WO1995031968A1 (en) |
Cited By (2)
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WO1998052579A1 (en) * | 1997-05-23 | 1998-11-26 | Insite Vision Incorporated | Ophthalmic compositions containing a divalent salt and a non steroidal anti-inflammatory drugs as a precipitate |
US11129812B2 (en) | 2016-08-19 | 2021-09-28 | Orasis Pharmaceuticals Ltd. | Ophthalmic pharmaceutical compositions and uses relating thereto |
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US6685958B2 (en) | 2001-04-25 | 2004-02-03 | Insite Vision Incorporated | Quinolone carboxylic acid compositions and related methods of treatment |
US6239113B1 (en) * | 1999-03-31 | 2001-05-29 | Insite Vision, Incorporated | Topical treatment or prevention of ocular infections |
US7056893B2 (en) | 1999-03-31 | 2006-06-06 | Insite Vision, Inc. | Topical treatment for prevention of ocular infections |
US6699492B2 (en) | 1999-03-31 | 2004-03-02 | Insite Vision Incorporated | Quinolone carboxylic acid compositions and related methods of treatment |
JP2003505180A (en) | 1999-08-02 | 2003-02-12 | ヘルセテック インコーポレイテッド | Metabolic calorimeter using respiratory gas analysis |
KR20120035220A (en) * | 2003-01-22 | 2012-04-13 | 센주 세이야꾸 가부시키가이샤 | Percutaneous absorption preparation for treating ophthalmic disease, use thereof and method for migration of ophthalmic remedy into topical tissue in eye |
US20060046970A1 (en) * | 2004-08-31 | 2006-03-02 | Insite Vision Incorporated | Topical otic compositions and methods of topical treatment of prevention of otic infections |
WO2006039659A1 (en) * | 2004-10-02 | 2006-04-13 | Sri International | Bioadhesive delivery system for transmucosal delivery of beneficial agents |
AR054336A1 (en) * | 2005-03-30 | 2007-06-20 | Astion Dev As | TREATMENT OF DERMATOLOGICAL AND PRURITE DISEASES |
CN101918019B (en) | 2007-10-08 | 2014-11-26 | 奥里尼亚制药有限公司 | Ophthalmic compositions comprising calcineurin inhibitors or mTOR inhibitors |
US20100247666A1 (en) * | 2009-03-24 | 2010-09-30 | Macleod Steven K | Method for Preparing Suspensions of Low-Solubility Materials |
US9775802B2 (en) | 2009-03-24 | 2017-10-03 | Bausch & Lomb Incorporated | Method for preparing suspensions of low-solubility materials |
AU2010259184B2 (en) | 2009-06-09 | 2015-08-13 | Aurinia Pharmaceuticals Inc. | Topical drug delivery systems for ophthalmic use |
US20190224275A1 (en) | 2017-05-12 | 2019-07-25 | Aurinia Pharmaceuticals Inc. | Protocol for treatment of lupus nephritis |
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JPS6056684B2 (en) * | 1977-11-07 | 1985-12-11 | 東興薬品工業株式会社 | eye drops |
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1994
- 1994-05-24 US US08/248,500 patent/US6309630B1/en not_active Expired - Lifetime
-
1995
- 1995-05-19 EP EP95919867A patent/EP0764018A1/en not_active Ceased
- 1995-05-19 JP JP53039895A patent/JP4158203B2/en not_active Expired - Lifetime
- 1995-05-19 CA CA002189424A patent/CA2189424C/en not_active Expired - Lifetime
- 1995-05-19 AU AU25529/95A patent/AU695699B2/en not_active Ceased
- 1995-05-19 WO PCT/US1995/006192 patent/WO1995031968A1/en not_active Application Discontinuation
Patent Citations (4)
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JPS58174309A (en) * | 1982-04-06 | 1983-10-13 | Wakamoto Pharmaceut Co Ltd | Antiphlogistic eye drop |
US4559343A (en) * | 1982-09-07 | 1985-12-17 | Alcon Laboratories, Inc. | Nonirritating aqueous ophthalmic compositions comfort formulation for ocular therapeutic agents |
US5296228A (en) * | 1992-03-13 | 1994-03-22 | Allergan, Inc. | Compositions for controlled delivery of pharmaceutical compounds |
WO1994010976A1 (en) * | 1992-11-16 | 1994-05-26 | Ciba Vision Ag, Hettlingen | Polyvinyl alcohol/borate ophthalmic drug delivery system |
Non-Patent Citations (3)
Title |
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PATENT ABSTRACTS OF JAPAN vol. 008, no. 007 (C - 204) 12 January 1984 (1984-01-12) * |
VULOVIC ET AL.: "Some studies into the properties of indomethacin suspensions intended for ophthalmic use", INT. J. PHARMACEUT., vol. 55, no. 2-3, pages 123 - 128 * |
WEISWEILER ET AL.: "Comparative comfort of flurbiprofen solution and indomethacin suspension eyedrops", J. CLIN. RES. DRUG DEVELOPMENT, vol. 2, no. 4, pages 233 - 239 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1998052579A1 (en) * | 1997-05-23 | 1998-11-26 | Insite Vision Incorporated | Ophthalmic compositions containing a divalent salt and a non steroidal anti-inflammatory drugs as a precipitate |
AU731175B2 (en) * | 1997-05-23 | 2001-03-22 | Insite Vision Incorporated | Ophthalmic compositions containing a divalent salt and a non steroidal anti-inflammatory drugs as a precipitate |
US6265444B1 (en) | 1997-05-23 | 2001-07-24 | Insite Vision Incorporated | Ophthalmic composition |
US11129812B2 (en) | 2016-08-19 | 2021-09-28 | Orasis Pharmaceuticals Ltd. | Ophthalmic pharmaceutical compositions and uses relating thereto |
Also Published As
Publication number | Publication date |
---|---|
CA2189424A1 (en) | 1995-11-30 |
AU2552995A (en) | 1995-12-18 |
US6309630B1 (en) | 2001-10-30 |
JPH10500684A (en) | 1998-01-20 |
AU695699B2 (en) | 1998-08-20 |
JP4158203B2 (en) | 2008-10-01 |
CA2189424C (en) | 2007-04-10 |
EP0764018A1 (en) | 1997-03-26 |
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