WO2004037267A1 - Method and composition containing latanoprost for treating ocular hypertension and glaucoma - Google Patents

Method and composition containing latanoprost for treating ocular hypertension and glaucoma Download PDF

Info

Publication number
WO2004037267A1
WO2004037267A1 PCT/JP2003/013452 JP0313452W WO2004037267A1 WO 2004037267 A1 WO2004037267 A1 WO 2004037267A1 JP 0313452 W JP0313452 W JP 0313452W WO 2004037267 A1 WO2004037267 A1 WO 2004037267A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
ophthalmic composition
ophthalmic
benzalkonium chloride
latanoprost
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2003/013452
Other languages
French (fr)
Inventor
Ryuji Ueno
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sucampo AG USA Inc
Original Assignee
Sucampo AG USA Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sucampo AG USA Inc filed Critical Sucampo AG USA Inc
Priority to DK03758746.6T priority Critical patent/DK1553953T3/en
Priority to CA2502437A priority patent/CA2502437C/en
Priority to DE60334134T priority patent/DE60334134D1/en
Priority to AU2003274734A priority patent/AU2003274734A1/en
Priority to AT03758746T priority patent/ATE480240T1/en
Priority to EP03758746A priority patent/EP1553953B1/en
Priority to JP2005501572A priority patent/JP2006503913A/en
Publication of WO2004037267A1 publication Critical patent/WO2004037267A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
    • A61K31/5575—Eicosanoids, e.g. leukotrienes or prostaglandins having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
    • 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
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • 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
    • A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
    • 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
    • A61P27/06—Antiglaucoma agents or miotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/186—Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin

Definitions

  • the present invention relates to a method and 5 composition for treating ocular hypertension and glaucoma with reduced side effects.
  • Preservatives used in ophthalmic composition are required to exhibit sufficient antimicrobial effect on 0' bacteria and fungi as well as high degree of safety such that inducing no or small affection on eye tissues such as corneal epithelium.
  • the preservatives themselves are required to be stable.
  • the preservatives are required to homogenize and stabilize the composition by interacting with the ingredients, for example, by homogeneously dispersing or dissolving the ingredients into the vehicle or base.
  • Benzalkonium chloride is a preservative most commonly used in commercially available ophthalmic solution.
  • preservatives are known as the major etiology of keratoconjunctive disorders, and for safety purpose, it is preferred that the concentration of a preservative such as benzalkonium chloride is below 0.01%.
  • a preservative such as benzalkonium chloride
  • preservatives contained in ophthalmic solution cause blood-aqueous barrier disruption and macular edema, especially cystoid macular edema (hereinafter referred to as "CME")- (The 105th General Assembly of Japan Ophthalmological Society, P.112, OSN Supersite, Top Stories, 97/10/02, the contents are herein incorporated by reference) .
  • Xalatan® ophthalmic solution which has been marketed as a drug for treating ocular hypertension and glaucoma, contains latanoprost as an active ingredient thereof.
  • Xalatan® ophthalmic solution contains benzalkonium chloride as a preservative at a concentration of 0.02% (package insert of Xalatan®) , and side effects such as keratoconjunctive disorders and CME caused by such high concentration of the preservative have been the problem.
  • latanoprost is highly fat-soluble, it has been believed to be difficult to prepare homogeneous and stable latanoprost ophthalmic composition without benzalkonium chloride.
  • latanoprost ophthalmic composition containing no or less than 0.02% of benzalkonium chloride has not been provided as a commercially available product.
  • the present invention relates to a method for treating ocular hypertension and glaucoma, which comprises administering an ophthalmic composition comprising latanoprost as an active ingredient thereof to a subject in need of said treatment, wherein the ophthalmic composition contains substantially no benzalkonium chloride.
  • the present invention relates to a method for treating ocular hypertension and glaucoma, which comprises administering an ophthalmic composition comprising latanoprost as an active ingredient thereof to a subject who has ocular hypertension and glaucoma and suffering from or is likely to suffer from keratoconjunctive disorders and/or macular edema, wherein the ophthalmic composition contains substantially no benzalkonium chloride. That is the method of the present invention is especially useful for a patient in need of the treatment or prevention of keratoconjunctive disorders and/or macular edema in addition to the treatment of ocular hypertension and glaucoma.
  • the present invention also relates to an ophthalmic composition for treating ocular hypertension and glaucoma comprising latanoprost as an active ingredient thereof, which contains substantially no benzalkonium chloride. Further, the present invention relates to use of latanoprost for manufacturing an ophthalmic composition for treating ocular hypertension and glaucoma, characterized in that the composition contains substantially no benzalkonium chloride.
  • the phrase of "the ophthalmic composition contains substantially no benzalkonium chloride" used herein means that the composition contains no benzalkonium chloride, or the composition contains benzalkonium chloride at a concentration that if the amount of benzalkonium chloride in the commercially available Xalatan® ophthalmic solution is reduced below said concentration, homogenous and/or stable solution is difficult to be prepared.
  • the ophthalmic composition may contain Benzalkonium chloride at a concentration of less than 0.02%, preferably 0.01% or less, more preferably 0.005% or less.
  • treatment or “treating” used herein includes any means of control such as prevention, care, relief of symptoms, attenuation of symptoms and arrest of progression.
  • the ophthalmic composition of the present invention may be formulated as any dosage form used in the ophthalmic field.
  • the ophthalmic composition may be in liquid form such as solution, emulsion and suspension or semisolid form such as gel and eye ointment.
  • Ophthalmic solution including emulsion and suspension as well as solution is preferably used.
  • the ingredients other than latanoprost may not be particularly limited as far as latanoprost is homogeneously and stably dispersed or dissolved in the composition.
  • Ophthalmic composition of the present invention may be manufactured according to any of conventional methods.
  • the composition may further contain a dissolving agent.
  • the dissolving agents used in the present invention may be any of conventionally used agents as far as it helps to disperse or dissolve latanoprost homogeneously and stably in an aqueous vehicle containing substantially no benzalkonium chloride.
  • dissolving agents may include polyoxyethylenesorbitan higher aliphatic acid monoester such as polysorbate 80, EDTA, boric acid, chlorhexidine gluconate, sodium persulfate, glycerol, concentrated glycerol, polyoxylated caster oil such as polyoxyethylene hydrogenated castor oil 40 and polyoxyethylene hydrogenated castor oil 60, polyoxyl stearate, macrogol, propyleneglycol, povidone, lower alcohol such as ethanol and chlorobutanol. Polysorbate 80 and EDTA are especially preferred.
  • the dissolving agent may be used solely or in combination with one or more other dissolving agents.
  • the ophthalmic composition of the present invention may further contain additives other than the above-listed dissolving agents.
  • the additives may be any of those conventionally used in the ophthalmic field.
  • the additives may include osmotic adjusting agents such as sodium chloride, potassium chloride, calcium chloride, sodium bicarbonate, sodium carbonate, magnesium sulfate, sodium hydrogen phosphate, sodium dihydrogen phosphate, dipotassium hydrogen phosphate, borax, sodium hydroxide, hydrochloric acid, isosorbitol, propylene glycol, mannitol, sucrose and glucose; buffering agents such as sodium monohydrogen phosphate and sodium dihydrogen phosphate; thickeners such as saccharides (e.g.
  • lactose and maltose lactose and maltose
  • hyaluronic acids or salt thereof e.g. sodium hyaluronate and potassium hyaluronate
  • mucopolysaccharides e.g. chondroitin sulfate
  • sodium polyacrylate carboxyvinyl polymer and crosslinked polyacrylate.
  • the composition may contain ordinarily used eye ointment bases in addition to the above additives.
  • eye ointment bases may include oil base such as Vaseline, liquid paraffin, polyethylene, Selen 50, Plastibase, macrogol and a combination thereof; emulsion base in which oil phase and aqueous phase have been emulsified with a surface active agent or the like; and water soluble base such as hydroxypropylmethylcellulose, carboxypropylcellulose and polyethylene glycol.
  • the present invention it is easy to prepare homogenous and stable latanoprost ophthalmic composition containing less than 0.02% of benzalkonium by admixing a dissolving agent.
  • the ophthalmic composition of the present invention may be prepared as a sterile unit dose type formulation for single use. Furthermore, since the ophthalmic composition of the present invention causes significantly fewer side effects such as keratoconjunctive disorders and CME than commercially available Xalatan® ophthalmic solution, the method or composition of the present invention provides more effective treatment to a subject suffering from keratoconjunctive disorder and/or macular edema such as CME .
  • the concentration of latanoprost in the composition and dosing frequency may vary according to the type of the subject such as species, age, sex, body weight and general health, symptoms to be treated, desired therapeutic effects, administration route, period of treatment and the like.
  • an ophthalmic solution containing latanoprost at a concentration of 0.00001 to 1%, preferably 0.0001 to 0.1%, more preferably 0.001 to 0.01% may be instilled 1 to 4 times, preferably 1 to 3 times, more preferably 1 to 2 times a day.
  • the composition may contain pharmaceutically active ingredients other than latanoprost as far as they are not contrary to the objects of the present invention.
  • the pharmaceutically active ingredients may include parasympathomimetic agents such as pilocarpine and carbachol; cholinesterase inhibitors such as physostigmine salicylate, distigmine bromide and echothiopate iodide; sympathomimetic agents such as epinephrine, dipivalylepinephrine, clonidine, p- aminoclonidine and brimonidine; ⁇ -adrenergic blockers such as betaxolol, levobunolol, timolol and carteolol; prostaglandin compounds such as isopropyl unoprostone, travoprost and bimatoprost; tropicamide and the like.
  • timolol is especially preferable.
  • the amount of each ingredient may be determined appropriately according to the therapeutic effects and safety of each ingredient.
  • Latanoprost was dispersed in sterilized water with various additives shown in table 1 below respectively to prepare 0.005% latanoprost ophthalmic solution. lOmL of each of the solution was agitated for seven hours and then stood still for 30 minutes. After that, the concentration of the latanoprost in the solutions was measured by HPLC and determined by internal standard method with one point calibration curve.

Landscapes

  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Diaphragms For Electromechanical Transducers (AREA)
  • Solid Thermionic Cathode (AREA)
  • Electrical Discharge Machining, Electrochemical Machining, And Combined Machining (AREA)

Abstract

Provided is an ophthalmic composition for treating ocular hypertension and glaucoma with reduced side effects such as keratoconjunctive disorders and macular edema. The composition comprises latanoprost as an active ingredient thereof and substantially no benzalkonium chloride. The composition of the invention especially useful for the treatment in a patient suffering from or is likely to suffer from keratoconjunctive disorders and/or macular edema.

Description

DESCRIPTION
METHOD AND COMPOSITION CONTAINING LATANOPROST FOR TREATING OCULAR HYPERTENSION AND GLAUCOMA
TECHNICAL FIELD
The present invention relates to a method and 5 composition for treating ocular hypertension and glaucoma with reduced side effects. BACKGROUND ART
Preservatives used in ophthalmic composition are required to exhibit sufficient antimicrobial effect on 0' bacteria and fungi as well as high degree of safety such that inducing no or small affection on eye tissues such as corneal epithelium. In addition to the original purposes as above, the preservatives themselves are required to be stable. Further, the preservatives are required to homogenize and stabilize the composition by interacting with the ingredients, for example, by homogeneously dispersing or dissolving the ingredients into the vehicle or base. Benzalkonium chloride is a preservative most commonly used in commercially available ophthalmic solution. However, preservatives are known as the major etiology of keratoconjunctive disorders, and for safety purpose, it is preferred that the concentration of a preservative such as benzalkonium chloride is below 0.01%. According to recent reports, preservatives contained in ophthalmic solution cause blood-aqueous barrier disruption and macular edema, especially cystoid macular edema (hereinafter referred to as "CME")- (The 105th General Assembly of Japan Ophthalmological Society, P.112, OSN Supersite, Top Stories, 97/10/02, the contents are herein incorporated by reference) .
Xalatan® ophthalmic solution, which has been marketed as a drug for treating ocular hypertension and glaucoma, contains latanoprost as an active ingredient thereof. Xalatan® ophthalmic solution contains benzalkonium chloride as a preservative at a concentration of 0.02% (package insert of Xalatan®) , and side effects such as keratoconjunctive disorders and CME caused by such high concentration of the preservative have been the problem.
However, since latanoprost is highly fat-soluble, it has been believed to be difficult to prepare homogeneous and stable latanoprost ophthalmic composition without benzalkonium chloride. To the present, latanoprost ophthalmic composition containing no or less than 0.02% of benzalkonium chloride has not been provided as a commercially available product. SUMMARY OF THE INVENTION
The present invention relates to a method for treating ocular hypertension and glaucoma, which comprises administering an ophthalmic composition comprising latanoprost as an active ingredient thereof to a subject in need of said treatment, wherein the ophthalmic composition contains substantially no benzalkonium chloride.
Especially, the present invention relates to a method for treating ocular hypertension and glaucoma, which comprises administering an ophthalmic composition comprising latanoprost as an active ingredient thereof to a subject who has ocular hypertension and glaucoma and suffering from or is likely to suffer from keratoconjunctive disorders and/or macular edema, wherein the ophthalmic composition contains substantially no benzalkonium chloride. That is the method of the present invention is especially useful for a patient in need of the treatment or prevention of keratoconjunctive disorders and/or macular edema in addition to the treatment of ocular hypertension and glaucoma.
The present invention also relates to an ophthalmic composition for treating ocular hypertension and glaucoma comprising latanoprost as an active ingredient thereof, which contains substantially no benzalkonium chloride. Further, the present invention relates to use of latanoprost for manufacturing an ophthalmic composition for treating ocular hypertension and glaucoma, characterized in that the composition contains substantially no benzalkonium chloride. The phrase of "the ophthalmic composition contains substantially no benzalkonium chloride" used herein means that the composition contains no benzalkonium chloride, or the composition contains benzalkonium chloride at a concentration that if the amount of benzalkonium chloride in the commercially available Xalatan® ophthalmic solution is reduced below said concentration, homogenous and/or stable solution is difficult to be prepared. In the present invention, the ophthalmic composition may contain Benzalkonium chloride at a concentration of less than 0.02%, preferably 0.01% or less, more preferably 0.005% or less.
The term "treatment" or "treating" used herein includes any means of control such as prevention, care, relief of symptoms, attenuation of symptoms and arrest of progression. DETAILED DESCRIPTION OF THE INVENTION
The ophthalmic composition of the present invention may be formulated as any dosage form used in the ophthalmic field. For example, the ophthalmic composition may be in liquid form such as solution, emulsion and suspension or semisolid form such as gel and eye ointment. Ophthalmic solution including emulsion and suspension as well as solution is preferably used. The ingredients other than latanoprost may not be particularly limited as far as latanoprost is homogeneously and stably dispersed or dissolved in the composition. Ophthalmic composition of the present invention may be manufactured according to any of conventional methods.
In case of the composition is an ophthalmic solution, the composition may further contain a dissolving agent. The dissolving agents used in the present invention may be any of conventionally used agents as far as it helps to disperse or dissolve latanoprost homogeneously and stably in an aqueous vehicle containing substantially no benzalkonium chloride. Examples of the dissolving agents may include polyoxyethylenesorbitan higher aliphatic acid monoester such as polysorbate 80, EDTA, boric acid, chlorhexidine gluconate, sodium persulfate, glycerol, concentrated glycerol, polyoxylated caster oil such as polyoxyethylene hydrogenated castor oil 40 and polyoxyethylene hydrogenated castor oil 60, polyoxyl stearate, macrogol, propyleneglycol, povidone, lower alcohol such as ethanol and chlorobutanol. Polysorbate 80 and EDTA are especially preferred. The dissolving agent may be used solely or in combination with one or more other dissolving agents.
The ophthalmic composition of the present invention may further contain additives other than the above-listed dissolving agents. According to the present invention, the additives may be any of those conventionally used in the ophthalmic field. Examples of the additives may include osmotic adjusting agents such as sodium chloride, potassium chloride, calcium chloride, sodium bicarbonate, sodium carbonate, magnesium sulfate, sodium hydrogen phosphate, sodium dihydrogen phosphate, dipotassium hydrogen phosphate, borax, sodium hydroxide, hydrochloric acid, isosorbitol, propylene glycol, mannitol, sucrose and glucose; buffering agents such as sodium monohydrogen phosphate and sodium dihydrogen phosphate; thickeners such as saccharides (e.g. lactose and maltose), hyaluronic acids or salt thereof (e.g. sodium hyaluronate and potassium hyaluronate) , mucopolysaccharides (e.g. chondroitin sulfate), sodium polyacrylate, carboxyvinyl polymer and crosslinked polyacrylate.
When the composition is an eye ointment, the composition may contain ordinarily used eye ointment bases in addition to the above additives. Examples of eye ointment bases may include oil base such as Vaseline, liquid paraffin, polyethylene, Selen 50, Plastibase, macrogol and a combination thereof; emulsion base in which oil phase and aqueous phase have been emulsified with a surface active agent or the like; and water soluble base such as hydroxypropylmethylcellulose, carboxypropylcellulose and polyethylene glycol.
According to the present invention, it is easy to prepare homogenous and stable latanoprost ophthalmic composition containing less than 0.02% of benzalkonium by admixing a dissolving agent. The ophthalmic composition of the present invention may be prepared as a sterile unit dose type formulation for single use. Furthermore, since the ophthalmic composition of the present invention causes significantly fewer side effects such as keratoconjunctive disorders and CME than commercially available Xalatan® ophthalmic solution, the method or composition of the present invention provides more effective treatment to a subject suffering from keratoconjunctive disorder and/or macular edema such as CME .
The concentration of latanoprost in the composition and dosing frequency may vary according to the type of the subject such as species, age, sex, body weight and general health, symptoms to be treated, desired therapeutic effects, administration route, period of treatment and the like. For example, an ophthalmic solution containing latanoprost at a concentration of 0.00001 to 1%, preferably 0.0001 to 0.1%, more preferably 0.001 to 0.01% may be instilled 1 to 4 times, preferably 1 to 3 times, more preferably 1 to 2 times a day.
In the present invention, the composition may contain pharmaceutically active ingredients other than latanoprost as far as they are not contrary to the objects of the present invention. Examples of the pharmaceutically active ingredients may include parasympathomimetic agents such as pilocarpine and carbachol; cholinesterase inhibitors such as physostigmine salicylate, distigmine bromide and echothiopate iodide; sympathomimetic agents such as epinephrine, dipivalylepinephrine, clonidine, p- aminoclonidine and brimonidine; β-adrenergic blockers such as betaxolol, levobunolol, timolol and carteolol; prostaglandin compounds such as isopropyl unoprostone, travoprost and bimatoprost; tropicamide and the like. Among these pharmaceutically active agents, timolol is especially preferable. In the preparation that contains two or more active ingredients, the amount of each ingredient may be determined appropriately according to the therapeutic effects and safety of each ingredient. The present invention will be described in more detail with reference to the following examples, which is not intended to limit the scope of the present invention. EXAMPLE
Latanoprost was dispersed in sterilized water with various additives shown in table 1 below respectively to prepare 0.005% latanoprost ophthalmic solution. lOmL of each of the solution was agitated for seven hours and then stood still for 30 minutes. After that, the concentration of the latanoprost in the solutions was measured by HPLC and determined by internal standard method with one point calibration curve.
Concentration of latanoprost (mg/mL) =
0.004 X Wς X
Qs
Ws: The amount of latanoprost in the standard preparation (mg)
Qs: Peak area ratio of latanoprost in the standard preparation to the internal standard
Qt: Peak area ratio of latanoprost in the test preparation to the internal standard
The results are shown in Table 1 below. Table 1. Concentration of latanoprost in the various latanoprost ophthalmic solution
Figure imgf000010_0001
*1) BAC: Benzalkonium chloride
*2) P80: polysorbate 80
*3) concentration of latanoprost
*4) ratio (%) of latanoprost in the solutions 30 minutes after the agitation for seven hours to initially used latanoprost
As is shown in Test Nos. 1 and 2, the homogeneity of latanoprost in the ophthalmic solution without benzalkonium chloride was improved by admixing polysorbate 80 (88.3% to 100 . 0% ) .
As is shown in Test Nos. 3-5 of Table 1, the homogeneity of latanoprost in the ophthalmic solution with 0.01% of benzalkonium chloride was improved by admixing polysorbate 80 or, polysorbate 80 and EDTA (97.3% to 99.9%).
These results suggested that the homogeneity and stability of latanoprost ophthalmic solution were improved by admixing a dissolving agent.

Claims

1. A method for treating ocular hypertension and glaucoma, which comprises administration of an ophthalmic composition comprising latanoprost as an active ingredient thereof to a subject in need of said treatment, wherein the ophthalmic composition contains substantially no benzalkonium chloride.
2. The method as described in Claim 1, wherein the ophthalmic composition contains a dissolving agent.
3. The method as described in Claim 2, wherein the dissolving agent is polysorbate 80 and/or EDTA.
4. The method as described in Claim 1, wherein the concentration of benzalkonium chloride is less than 0.02%.
5. The method as described in Claim 1, wherein the concentration of benzalkonium chloride is 0.01% or less.
6. The method as described in Claim 1, wherein the ophthalmic composition is formulated as a single-unit dose preparation.
7. The method as described in Claim 1, wherein the ophthalmic composition further comprises timolol.
8. The method as described in Claim 1, wherein the ophthalmic composition is an ophthalmic solution.
9. A method for treating ocular hypertension and glaucoma, which comprises administration of an ophthalmic composition comprising latanoprost as an active ingredient thereof to a subject who has ocular hypertension and glaucoma and also has or is likely to have keratoconjunctive disorders and/or macular edema, wherein the ophthalmic composition contains substantially no benzalkonium chloride.
10. The method as described in Claim 9, wherein the ophthalmic composition contains a dissolving agent.
11. The method as described in Claim 10, wherein the dissolving agent is polysorbate 80 and/or EDTA.
12. The method as described in Claim 9, wherein the concentration of benzalkonium chloride is less than 0.02%.
13. The method as described in Claim 9, wherein the concentration of benzalkonium chloride is 0.01% or less.
14. The method as described in Claim 9, wherein the ophthalmic composition is formulated as a single-unit dose preparation.
15. The method as described in Claim 9, wherein the ophthalmic composition further comprises timolol.
16. The method as described in Claim 9, wherein the ophthalmic composition is an ophthalmic solution.
17. An ophthalmic composition for treating ocular hypertension and glaucoma comprising latanoprost as an active ingredient thereof, which contains substantially no benzalkonium chloride.
18. The composition as described in Claim 17, wherein the ophthalmic composition contains a dissolving agent.
19. The composition as described in Claim 18, wherein the dissolving agent is polysorbate 80 and/or EDTA.
20. The composition as described in Claim 17, wherein the concentration of benzalkonium chloride is less than 0.02%.
21. The composition as described in Claim 17, wherein the concentration of benzalkonium chloride is 0.01% or less.
22. The composition as described in Claim 17, wherein the ophthalmic composition is formulated as a single-unit dose preparation.
23. The composition as described in Claim 17, wherein the ophthalmic composition further comprises timolol.
24. The composition as described in Claim 17, wherein the ophthalmic composition is an ophthalmic solution.
25. An ophthalmic composition for treating ocular hypertension and glaucoma in a patient suffering from or is likely to suffer from keratoconjunctive disorders and/or macular edema, comprising latanoprost as an active ingredient thereof, wherein the ophthalmic composition contains substantially no benzalkonium chloride.
26. The composition as described in Claim 25, wherein the ophthalmic composition contains a dissolving agent.
27. The composition as described in Claim 26, wherein e dissolving agent is polysorbate 80 and/or EDTA.
28. The composition as described in Claim 25, wherein the concentration of benzalkonium chloride is less than 0.02%.
29. The composition as described in Claim 25, wherein the concentration of benzalkonium chloride is 0.01% or less.
30. The composition as described in Claim 25, wherein the ophthalmic composition is formulated as a single-unit dose preparation.
31. The composition as described in Claim 25, wherein the ophthalmic composition further comprises timolol.
32. The composition as described in Claim 25, wherein the ophthalmic composition is an ophthalmic solution.
33. Use of latanoprost for manufacturing an ophthalmic composition for treating ocular hypertension and glaucoma, characterized in that the composition comprises substantially no benzalkonium chloride.
34. The use as described in Claim 33, wherein the ophthalmic composition contains a dissolving agent.
35. The use as described in Claim 34, wherein the dissolving agent is polysorbate 80 and/or EDTA.
36. The use as described in Claim 33, wherein the concentration of benzalkonium chloride is less than 0.02%.
37. The use as described in Claim 33, wherein the concentration of benzalkonium chloride is 0.01% or less.
38. The use as described in Claim 33, wherein the ophthalmic composition is formulated as a single-unit dose preparation.
39. The use as described in Claim 33, wherein the ophthalmic composition further comprises timolol.
40. The use as described in Claim 33, wherein the ophthalmic composition is an ophthalmic solution.
41. Use of latanoprost for manufacturing an ophthalmic composition for treating ocular hypertension and glaucoma in a patient, characterized in that said patient suffering from or is likely to suffer from keratoconjunctive disorders and/or macular edema and that the ophthalmic composition contains substantially no benzalkonium chloride.
42. The use as described in Claim 41, wherein the ophthalmic composition contains a dissolving agent.
43. The use as described in Claim 42, wherein the dissolving agent is polysorbate 80 and/or EDTA.
44. The use as described in Claim 41, wherein the concentration of benzalkonium chloride is less than 0.02%.
45. The use as described in Claim 41, wherein the concentration of benzalkonium chloride is 0.01% or less.
46. The use as described in Claim 41, wherein the ophthalmic composition is formulated as a single-unit dose preparation.
47. The use as described in Claim 41, wherein the ophthalmic composition further comprises timolol.
48. The use as described in Claim 41, wherein the ophthalmic composition is an ophthalmic solution.
PCT/JP2003/013452 2002-10-24 2003-10-22 Method and composition containing latanoprost for treating ocular hypertension and glaucoma Ceased WO2004037267A1 (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
DK03758746.6T DK1553953T3 (en) 2002-10-24 2003-10-22 A method and composition comprising latanoprost for the treatment of ocular hypertension and glaucoma
CA2502437A CA2502437C (en) 2002-10-24 2003-10-22 Method and composition containing latanoprost for treating ocular hypertension and glaucoma
DE60334134T DE60334134D1 (en) 2002-10-24 2003-10-22 UNGSMETHOD OF INCREASED AUGENINNENDRUCK AND GLAUKOM
AU2003274734A AU2003274734A1 (en) 2002-10-24 2003-10-22 Method and composition containing latanoprost for treating ocular hypertension and glaucoma
AT03758746T ATE480240T1 (en) 2002-10-24 2003-10-22 COMPOSITION CONTAINING LATANOPROST AND METHOD OF TREATMENT OF INCREASED EYE PRESSURE AND GLAUCOMA
EP03758746A EP1553953B1 (en) 2002-10-24 2003-10-22 Method and composition containing latanoprost for treating ocular hypertension and glaucoma
JP2005501572A JP2006503913A (en) 2002-10-24 2003-10-22 Methods and latanoprost-containing compositions for the treatment of ocular hypertension and glaucoma

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US42077602P 2002-10-24 2002-10-24
US60/420,776 2002-10-24
US42104402P 2002-10-25 2002-10-25
US60/421,044 2002-10-25
US10/429,677 2003-05-06
US10/429,677 US7074827B2 (en) 2002-10-24 2003-05-06 Method for treating ocular hypertension and glaucoma

Publications (1)

Publication Number Publication Date
WO2004037267A1 true WO2004037267A1 (en) 2004-05-06

Family

ID=32110845

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2003/013452 Ceased WO2004037267A1 (en) 2002-10-24 2003-10-22 Method and composition containing latanoprost for treating ocular hypertension and glaucoma

Country Status (9)

Country Link
US (2) US7074827B2 (en)
EP (2) EP1553953B1 (en)
JP (2) JP2006503913A (en)
AT (1) ATE480240T1 (en)
AU (1) AU2003274734A1 (en)
CA (1) CA2502437C (en)
DE (1) DE60334134D1 (en)
DK (1) DK1553953T3 (en)
WO (1) WO2004037267A1 (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2269575A1 (en) 2009-06-30 2011-01-05 Santen Pharmaceutical Co., Ltd Method for improving bioavailability of latanoprost
US8722735B2 (en) 2008-03-17 2014-05-13 Alcon Research, Ltd. Pharmaceutical compositions having desirable bioavailability
US9999593B2 (en) 2008-05-30 2018-06-19 Santen Pharmaceutical Co., Ltd. Method and composition for treating ocular hypertension and glaucoma

Families Citing this family (66)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2004283091A1 (en) * 2003-10-03 2005-05-06 Allergan, Inc. Compositions and methods comprising prostaglandin-related compounds and trefoil factor family peptides for the treatment of glaucoma with reduced hyperemia
DE602004017477D1 (en) * 2004-11-09 2008-12-11 Novagali Pharma Sa Oil-in-water emulsion with low concentration of cationic agent and positive zeta potential
GB0501192D0 (en) * 2005-01-20 2005-03-02 Resolution Chemicals Ltd Stable prostaglandin-containing compositions
DE102005035986B4 (en) * 2005-07-28 2009-10-15 Bausch & Lomb Incorporated Sterile drippable multiphase emulsifier-free ophthalmic preparation
PT1937212E (en) * 2005-10-10 2010-11-30 Novagali Pharma Sa Ophthalmic emulsions containing prostaglandins
US7666912B2 (en) * 2006-03-23 2010-02-23 Massachusetts Eye And Ear Infirmary Compositions and methods for reducing body fat
TWI394564B (en) * 2006-09-21 2013-05-01 Alcon Res Ltd Self-preserved aqueous pharmaceutical compositions
KR101421519B1 (en) * 2006-09-28 2014-07-30 알콘 리서치, 리미티드 Self-preserved aqueous pharmaceutical compositions
FR2912207B1 (en) * 2007-02-01 2012-10-26 Air Liquide PROCESS AND APPARATUS FOR PRODUCING CARBON MONOXIDE BY CRYOGENIC DISTILLATION
WO2008096804A1 (en) * 2007-02-07 2008-08-14 Teika Pharmaceutical Co., Ltd. Eye drop preparation comprising latanoprost
JP2008247828A (en) * 2007-03-30 2008-10-16 Wakamoto Pharmaceut Co Ltd An aqueous pharmaceutical composition containing latanoprost.
FR2918891B1 (en) * 2007-07-20 2009-09-25 Thea Sa Lab OPHTHALMIC SOLUTION BASED ON PROSTAGLANDINS WITHOUT PRESERVATIVE
JP2009040727A (en) * 2007-08-09 2009-02-26 Towa Yakuhin Kk Stable eye lotion containing latanoprost as active ingredient
EP2193795B1 (en) * 2007-08-29 2014-10-01 Wakamoto Pharmaceutical Co., Ltd. Latanoprost-containing aqueous pharmaceutical composition
MX2007011165A (en) * 2007-09-12 2009-03-11 Arturo Jimenez Bayardo Pharmaceutically stable compound consisting of timolol, dorzolamide and brimonidine.
ES2638771T3 (en) * 2008-03-17 2017-10-24 Novartis Ag Aqueous pharmaceutical compositions containing borate-polyol complexes
EP2228058A1 (en) 2009-03-04 2010-09-15 Novagali Pharma S.A. Anionic oil-in-water emulsion containing prostaglandins and uses thereof
US10206813B2 (en) 2009-05-18 2019-02-19 Dose Medical Corporation Implants with controlled drug delivery features and methods of using same
US12478503B2 (en) 2009-05-18 2025-11-25 Glaukos Corporation Implants with controlled drug delivery features and methods of using same
WO2010135731A1 (en) * 2009-05-22 2010-11-25 Kaufman Herbert E Preparations and methods for ameliorating or reducing presbyopia
US8299079B2 (en) 2009-05-22 2012-10-30 Kaufman Herbert E Preparations and methods for ameliorating or reducing presbyopia
JP2010275259A (en) * 2009-05-29 2010-12-09 Toa Yakuhin Kk Uniform and stable latanoprost ophthalmic liquid composition
TWI489997B (en) * 2009-06-19 2015-07-01 Alcon Res Ltd Aqueous pharmaceutical compositions containing borate-polyol complexes
EP2389939A1 (en) 2010-05-28 2011-11-30 Novagali Pharma S.A. Use of prostaglandins F2alpha and analogues for the healing of corneal and conjunctival lesions
WO2011113855A2 (en) 2010-03-17 2011-09-22 Novaliq Gmbh Pharmaceutical composition for treatment of increased intraocular pressure
FR2961694B1 (en) * 2010-06-29 2013-01-25 Thea Lab POLYMERIC DELIVERY SYSTEM FOR NON-VISCOUS SOLUTION BASED ON PROSTAGLANDIN WITHOUT PRESERVATIVE
US9061034B2 (en) 2010-07-29 2015-06-23 Allergan, Inc. Preservative free bimatoprost and timolol solutions
US9078854B2 (en) 2010-07-29 2015-07-14 Allergan, Inc. Preservative free bimatoprost and timolol solutions
CA2806973A1 (en) * 2010-07-29 2012-02-02 Allergan, Inc. Preservative free bimatoprost solutions
EP2452669A1 (en) 2010-10-29 2012-05-16 Omnivision GmbH Ophthalmic composition
EP2462921A1 (en) 2010-11-11 2012-06-13 Novaliq GmbH Liquid pharmaceutical compositions for the treatment of a posterior eye disease
ES2687494T3 (en) 2011-01-19 2018-10-25 Topokine Therapeutics, Inc. Methods and compositions to reduce body fat
US8426471B1 (en) 2011-12-19 2013-04-23 Topokine Therapeutics, Inc. Methods and compositions for reducing body fat and adipocytes
JP6329130B2 (en) * 2012-04-10 2018-05-30 アイノビア，インコーポレイティド Spray ejector mechanism, device that provides charge separation and controllable droplet charge, and low dose eye drops
EP2838669B1 (en) 2012-04-20 2018-01-03 Eyenovia, Inc. Spray ejector device and methods of use
WO2013173321A1 (en) 2012-05-14 2013-11-21 Corinthian Ophthalmic, Inc. Laminar flow droplet generator device and methods of use
EA201492094A1 (en) 2012-05-15 2015-04-30 Айновиа, Инк. EJECTOR DEVICES, METHODS, PATTERNS AND SCHEMES FOR THEM
CN113679697A (en) 2012-09-12 2021-11-23 诺瓦利克有限责任公司 Compositions comprising mixtures of semifluorinated alkanes
DK3181119T3 (en) 2012-09-12 2019-09-16 Novaliq Gmbh SEMIFLUORED ALKAN COMPOSITIONS TO USE IN TREATMENT OF KERATOCONJUNCTIVITIS SICCA
WO2014081941A1 (en) 2012-11-21 2014-05-30 Topokine Therapeutics, Inc. Methods and compositions for locally increasing body fat
WO2014159679A1 (en) 2013-03-12 2014-10-02 The United States Of America, As Represented By The Secretary, Department Of Health & Human Services Methods for using lubiprostone to absorb fluid from the subretinal space
NO2753788T3 (en) 2013-05-10 2018-06-16
WO2014186504A1 (en) 2013-05-15 2014-11-20 Topokine Therapeutics, Inc. Methods and compositions for topical delivery of prostaglandins to subcutaneous fat
WO2015029923A1 (en) * 2013-08-26 2015-03-05 ロート製薬株式会社 Ophthalmological preparation
GR1008483B (en) * 2013-12-23 2015-05-12 Rafarm Α.Ε.Β.Ε., Ophthalmic pharmaceutiacl composition and process for the preparation thereof
US10188661B2 (en) 2014-06-27 2019-01-29 Topokine Therapeutics, Inc. Topical dosage regimen
JP6604328B2 (en) 2014-08-05 2019-11-13 ソニー株式会社 DC power transmission device, DC power reception device, and DC power transmission system
MX2018003781A (en) 2015-09-30 2018-09-12 Novaliq Gmbh Semifluorinated compounds for ophthalmic administration.
CN108348777B (en) 2015-09-30 2020-04-28 诺瓦利克有限责任公司 Semifluorinated compounds and compositions thereof
GR1009040B (en) * 2016-04-19 2017-05-19 Φαρματεν Ανωνυμος Βιομηχανικη Και Εμπορικη Εταιρεια Φαρμακευτικων Ιατρικων Και Καλλυντικων Προϊοντων Preservative free pharmaceutical ophthalmic compositions
USRE50060E1 (en) 2016-06-23 2024-07-30 Novaliq Gmbh Topical administration method
ES2969758T3 (en) 2016-09-22 2024-05-22 Novaliq Gmbh Pharmaceutical compositions for use in the therapy of blepharitis
US10813976B2 (en) 2016-09-23 2020-10-27 Novaliq Gmbh Ophthalmic compositions comprising ciclosporin
PT3399962T (en) 2016-12-23 2020-09-03 Novaliq Gmbh Ophthalmic composition for treatment of dry eye disease
US11278503B2 (en) 2017-05-12 2022-03-22 Novaliq Gmbh Pharmaceutical compositions comprising semifluorinated alkanes for the treatment of contact lense-related conditions
KR20200059272A (en) 2017-09-27 2020-05-28 노바리크 게엠베하 Ophthalmic composition comprising latanoprost for use in the treatment of ocular diseases
CN111182893A (en) 2017-10-04 2020-05-19 诺瓦利克有限责任公司 Ophthalmic composition comprising F6H8
EP3758676A1 (en) 2018-03-02 2021-01-06 Novaliq GmbH Pharmaceutical compositions comprising nebivolol
KR102882058B1 (en) 2018-03-28 2025-11-07 노바리크 게엠베하 Pharmaceutical composition containing timolol
JP2021522219A (en) 2018-04-27 2021-08-30 ノバリック ゲーエムベーハー Ophthalmic composition containing tafluprost for the treatment of glaucoma
SG11202102820VA (en) 2018-10-12 2021-04-29 Novaliq Gmbh Ophthalmic composition for treatment of dry eye disease
CN113710228A (en) 2019-02-13 2021-11-26 诺瓦利克有限责任公司 Compositions and methods for treating ocular neovascularization
US12539302B2 (en) 2019-08-07 2026-02-03 Aneira Pharma, Inc. Methods and compositions for the treatment of hair loss
EP4331683A3 (en) 2019-08-07 2024-08-07 Aneira Pharma, Inc. Methods and compositions for the treatment of hair loss
US12419933B2 (en) 2019-09-06 2025-09-23 Novaliq Gmbh Ophthalmic composition for the treatment of uveitis
JP2022120120A (en) * 2022-06-13 2022-08-17 東亜薬品株式会社 OPHTHALMOLOGIC AQUEOUS COMPOSITION AND METHOD FOR INHIBITING DECREASE IN CONTENT OF PROSTAGLANDIN F2α DERIVATIVE

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001095913A1 (en) 2000-06-13 2001-12-20 Synphora Ab Methods and compositions for the prevention of myopia
WO2002038158A1 (en) 2000-11-13 2002-05-16 Pharmacia Ab Improved treatment
US20020103255A1 (en) 1997-12-19 2002-08-01 Hellberg Mark R. Use of non-steroidal anti-inflammatory agents in combination with prostaglandin FP receptor agonists to treat glaucoma and ocular hypertension
EP1532981A1 (en) 2002-08-23 2005-05-25 Santen Pharmaceutical Co., Ltd. Stable eye drops containing latanoprost as the active ingredient

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1300150T1 (en) * 1988-09-06 2003-09-18 Pharmacia Ab, Stockholm Prostaglandin derivatives used to treat glaucoma or hypertension
US5296504A (en) * 1988-09-06 1994-03-22 Kabi Pharmacia Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension
AU665287B2 (en) 1992-12-21 1995-12-21 Alcon Laboratories, Inc. Prostaglandin combinations in glaucoma therapy
AU7680096A (en) 1995-12-22 1997-07-17 Alcon Laboratories, Inc. Combinations of dp and fp type prostaglandins for lowering iop
JPH10259179A (en) * 1996-09-19 1998-09-29 Santen Pharmaceut Co Ltd Prostaglandins having polysubstituted aryloxy groups and uses thereof
AR002194A1 (en) 1997-03-17 1998-01-07 Sanchez Reynaldo Alemany COMPUTERIZED INSTRUMENT FOR THE ANALYSIS OF MOVEMENT.
JP4000505B2 (en) * 1999-12-01 2007-10-31 第一三共株式会社 Concomitant medications for treating glaucoma
US20020035148A1 (en) * 2000-07-20 2002-03-21 Ryuji Ueno Treatment of ocular hypertension
JP3876355B2 (en) * 2000-09-13 2007-01-31 参天製薬株式会社 Ophthalmic solution
CA2422031C (en) * 2000-09-13 2011-11-15 Santen Pharmaceutical Co., Ltd. Ophthalmic solutions comprising difluoroprostaglandin f2 alpha
US8549114B2 (en) * 2002-06-12 2013-10-01 Bladelogic, Inc. Method and system for model-based heterogeneous server configuration management
CA2707067C (en) * 2002-09-09 2013-07-16 Santen Pharmaceutical Co., Ltd. Clear ophthalmic solution comprising latanoprost as active ingredient

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020103255A1 (en) 1997-12-19 2002-08-01 Hellberg Mark R. Use of non-steroidal anti-inflammatory agents in combination with prostaglandin FP receptor agonists to treat glaucoma and ocular hypertension
WO2001095913A1 (en) 2000-06-13 2001-12-20 Synphora Ab Methods and compositions for the prevention of myopia
WO2002038158A1 (en) 2000-11-13 2002-05-16 Pharmacia Ab Improved treatment
EP1532981A1 (en) 2002-08-23 2005-05-25 Santen Pharmaceutical Co., Ltd. Stable eye drops containing latanoprost as the active ingredient

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
COSTAGLIOLA C ET AL: "Ocular surface changes induced by topical application of latanoprost and timolol: A short-term study in glaucomatous patients with and without allergic conjunctivitis", GRAEFE'S ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY 2001 GERMANY, vol. 239, no. 11, 2001, pages 809 - 814, XP002272140, ISSN: 0721-832X *
COSTAGLIOLA ET AL., GRAEFE'S ARCH CLIN EXP OPHTHALMOL, vol. 239, 2001, pages 809 - 814

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8722735B2 (en) 2008-03-17 2014-05-13 Alcon Research, Ltd. Pharmaceutical compositions having desirable bioavailability
US8754123B2 (en) 2008-03-17 2014-06-17 Alcon Research, Ltd. Pharmaceutical compositions having desirable bioavailability
US9144561B2 (en) 2008-03-17 2015-09-29 Alcon Research, Ltd. Pharmaceutical compositions having desirable bioavailability
US9999593B2 (en) 2008-05-30 2018-06-19 Santen Pharmaceutical Co., Ltd. Method and composition for treating ocular hypertension and glaucoma
US10864159B2 (en) 2008-05-30 2020-12-15 Santen Pharmaceutical Co., Ltd. Method and composition for treating ocular hypertension and glaucoma
EP2269575A1 (en) 2009-06-30 2011-01-05 Santen Pharmaceutical Co., Ltd Method for improving bioavailability of latanoprost

Also Published As

Publication number Publication date
EP1553953B1 (en) 2010-09-08
DK1553953T3 (en) 2010-10-25
CA2502437C (en) 2012-07-17
US8673973B2 (en) 2014-03-18
AU2003274734A1 (en) 2004-05-13
US20060205725A1 (en) 2006-09-14
EP1553953A1 (en) 2005-07-20
JP2006503913A (en) 2006-02-02
ATE480240T1 (en) 2010-09-15
US7074827B2 (en) 2006-07-11
CA2502437A1 (en) 2004-05-06
JP2012162570A (en) 2012-08-30
EP2253322A1 (en) 2010-11-24
DE60334134D1 (en) 2010-10-21
US20040082660A1 (en) 2004-04-29

Similar Documents

Publication Publication Date Title
CA2502437C (en) Method and composition containing latanoprost for treating ocular hypertension and glaucoma
US6271224B1 (en) Use of certain isoquinolinesulfonyl compounds for the treatment of glaucoma and ocular ischemia
RU2563125C2 (en) Aqueous pharmaceutical compositions, containing borate-polyol complexes
US10792288B2 (en) Preservative free brimonidine and timolol solutions
US20100041671A1 (en) Methods for treating glaucoma
EP2316420B1 (en) Topical ophthalmic composition to reduce pain
KR20140056280A (en) Fixed dose combination of bimatoprost and brimonidine
US5438060A (en) Method of reducing elevated intraocular pressure
CA2274708A1 (en) Remedial composition for intraocular hypertension or glaucoma
EP1283043A1 (en) Ophthalmic solution
EP0205606B1 (en) Pharmaceutical compositions and their use as mydriatics
JP6963651B2 (en) Aqueous composition containing epinastine or a salt thereof
KR20230145458A (en) Aqueous pharmaceutical composition containing ursodeoxycholic acid or its salt
KR20220089106A (en) Eye drop composition comprising corzolamide or polysorbate 80 as an active ingredient
JPWO2000038689A1 (en) Pharmaceutical composition for treating ocular hypertension or glaucoma
EP0728480A1 (en) Use of ifenprodil for treatment of elevated intraocular pressure
US20240165147A1 (en) Methods for Treating Eyetear Film Deficiency
JP7118579B1 (en) Aqueous composition containing epinastine or its salt
ES2349699T3 (en) METHOD AND COMPOSITION CONTAINING LATANOPROST TO TREAT EYE HYPERTENSION AND GLAUCOMA.
WO2025108987A1 (en) Compositions and methods for treating eyetear film deficiency and redeye
WO2024034592A1 (en) Aqueous pharmaceutical composition containing udca or salt thereof
KR20250126761A (en) Aqueous composition containing epinastine for improving tissue transportability and antiseptic effect
WO2019123266A1 (en) Ophthalmic composition having a prostaglandin and a beta-blocker
WO2000043015A1 (en) Eye drops
WO1996007406A1 (en) Combination of levobunolol and dipivefrin for ophthalmic use

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

WWE Wipo information: entry into national phase

Ref document number: 2003758746

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 2005501572

Country of ref document: JP

121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 2502437

Country of ref document: CA

WWP Wipo information: published in national office

Ref document number: 2003758746

Country of ref document: EP