WO1999000133A1 - Procede permettant d'optimiser l'etat de sante de la retine et du nerf optique - Google Patents

Procede permettant d'optimiser l'etat de sante de la retine et du nerf optique

Info

Publication number
WO1999000133A1
WO1999000133A1 PCT/US1998/013038 US9813038W WO9900133A1 WO 1999000133 A1 WO1999000133 A1 WO 1999000133A1 US 9813038 W US9813038 W US 9813038W WO 9900133 A1 WO9900133 A1 WO 9900133A1
Authority
WO
WIPO (PCT)
Prior art keywords
adrenergic receptor
carbonic anhydrase
composition
solution
anhydrase inhibitor
Prior art date
Application number
PCT/US1998/013038
Other languages
English (en)
Inventor
Michael S. Sugrue
Original Assignee
Merck & Co., 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
Priority claimed from GBGB9800449.2A external-priority patent/GB9800449D0/en
Application filed by Merck & Co., Inc. filed Critical Merck & Co., Inc.
Priority to EP98931510A priority Critical patent/EP1024810A4/fr
Priority to AU81622/98A priority patent/AU740874B2/en
Priority to CA002294343A priority patent/CA2294343A1/fr
Priority to JP50566199A priority patent/JP2002506461A/ja
Publication of WO1999000133A1 publication Critical patent/WO1999000133A1/fr

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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—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 sulfur as the ring hetero atoms, e.g. sulthiame
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • 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

Definitions

  • Glaucoma is a degenerative disease of the eye wherein the intraocular pressure is too high to permit normal eye function. As a result, damage may occur to the optic nerve head and result in irreversible loss of visual function. If untreated, glaucoma may eventually lead to blindness.
  • Ocular hypertension i.e., the condition of elevated intraocular pressure without optic nerve head damage or characteristic glaucomatous visual field defects, is now believed by the majority of ophthalmologists to represent merely the earliest phase in the onset of glaucoma.
  • Normal tension glaucoma is the condition where there is no elevated intraocular pressure.
  • glaucoma may have a vascular component, possibly vasospastic.
  • New scientific technologies allow us to look more at the back of the eye and evaluate glaucoma from a circulatory, metabolic and hematological angle, therefore, being better able to determine the cause of the disease.
  • the light beam After the light beam has been processed in the photoreceptor disks, it passes back through the cilium, the ellipsoid, myoid, Mueller cells, outer fiber, nucleus, inner fiber, synaptic vesicle, the other plexiform layer, inner nuclear layer, the bipolar cells, the inner plexiform layer, finally reaching the ganglion cells where it is processed into an axon signal. After it reaches the ganglion cells, the signal is transported through the optic nerve fibers to the brain where it is assessed and compounded by the visual brain lobes to form the visual picture.
  • Glaucoma is seen as the progressive loss of optic nerve axons which leads to an interrupted signal flow, therefore, the result is visual field damage which leads over longer periods of time to blindness.
  • TRUSOPT (dorzolamide HC1; MK507) is the active ingredient in TRUSOPT which is prescribed for the treatment of elevated intraocular pressure in ocular hypertension, open-angle glaucoma and pseudo-exfoliative glaucoma.
  • TRUSOPT (R) Ophthalmic Solution is applied as an isotonic, buffered, slightly viscous, aqueous solution of dorzolamide HC1.
  • Each ml of TRUSOPT® 2% contains 20 mg dorzolamide (22.3mg dorzolamide HC1). When used as monotherapy, the dose is one drop of
  • TRUSOPT (R) Ophthalmic Solution in the conjunctival sac of each affected eye three times daily.
  • the present invention is directed to a method for increasing retinal and optic nerve head blood velocity in a patient in need thereof by topical application of a composition comprising a hypotonic solution of xanthan gum and a topical carbonic anhydrase inhibitor.
  • the present invention is also directed to a method for maximizing the health of the optic nerve and retina by topical application of a composition comprising a hypotonic solution of xanthan gum and a topical carbonic anhydrase inhibitor.
  • the present invention is also directed to a method for treating normal tension glaucoma by topical application of a composition comprising a hypotonic solution of xanthan gum and a topical carbonic anhydrase inhibitor.
  • the invention relates to a method for increasing retinal and optic nerve head blood velocity by topical application of a composition comprising a topical carbonic anhydrase inhibitor(TCAI) such as those which are described in U.S. Patent Nos. 4,797,413, 4,386,098, 4,416,890, 4,426,388, 5,378,703, 5,240,923 and 5,153,192; and the like.
  • TCAI topical carbonic anhydrase inhibitor
  • Particularly preferred topical carbonic anhydrase inhibitors is the class of compounds of the structural formula (I):
  • A is carbon or nitrogen, preferably carbon
  • Z is -NHR or -OR, preferably -NHR;
  • R is C 1-6 alkyl, either straight or branched chain, preferably C 2 . 4 alkyl such as ethyl, propyl or isobutyl; R 1 is
  • the carbon atoms to which Z and R 1 are bonded may be chiral.
  • the first letter represents the chirality the carbon atom to which Z is bonded and the second letter represents the chirality of A when A is carbon.
  • the carbonic anhydrase inhibitors of this invention accordingly may be used as diastereomeric mixtures or single enantiomers or as racemic mixtures. More preferred carbonic anhydrase inhibitors are dorzolamide, brinzolamide, acetazolamide, metazolamide described in U.S.
  • the invention relates to a method for increasing retinal and optic nerve head blood velocity by topical application of a composition wherein the topical carbonic anhydrase inhibitor is (S,S)-(-)-5,6-dihydro-4-ethylamino-6-methyl-4H-thieno[2,3- b]thiopyran-2-sulphonamide-7,7-dioxide, or an ophthalmologically acceptable salt thereof or 2H-thieno[3,2-e]-l,2-thiazine-6-sulfonamide-4- (ethylamino)-3,4-dihydro-2-(3-methoxypropyl)-l,l-dioxide or an ophthalmologically acceptable salt thereof.
  • the topical carbonic anhydrase inhibitor is (S,S)-(-)-5,6-dihydro-4-ethylamino-6-methyl-4H-thieno[2,3- b]thiopyran-2-sulphonamide
  • the present invention is directed to a method for increasing retinal and optic nerve head blood velocity by topical application of a composition comprising a hypotonic solution of xanthan gum and a topical carbonic anhydrase inhibitor. It is also directed to a method for treating normal tension glaucoma by topical application of a composition comprising a hypotonic solution of xanthan gum and a topical carbonic anhydrase inhibitor.
  • the present invention is based upon the finding that CAIs can preserve or benefit vision by increasing both retinal and optic nerve head blood flow velocity. The increase in blood flow velocities was attained without any change in retinal vessel width which might have been the expected reason for the increase in flow velocity.
  • the concentration of xanthan gum comprises about 0.1 to 2% (w/w), preferably 0.4 to 0.7% (w/w). Particularly preferred is KELTROLTM T xanthan gum from Monsanto Performance Materials.
  • Xanthan gum is a high molecular weight polysaccharide gum obtainable from the aerobic fermentation of a carbohydrate with bacteria of the genus Xanthomonas, especially Xanthomonas campestris.
  • Each xanthan gum repeat unit contains five sugar residues: two glucose, two mannose and one glucuronic acid.
  • the polymer backbone consists of four ⁇ -D-glucose units linked at the 1 and 4 positions. Trisaccharide side chains on alternating anhydroglucose units distinguish xanthan gum from cellulose. Each side chain comprises a glucuronic acid residue between two mannose units. At most of the terminal mannose units is a pyruvate moiety.
  • Xanthan gum solutions are pseudoplastic. In other words, when shear stress is increased, the viscosity is progressively reduced. Upon reduction of the shear, total viscosity is recovered almost instantaneously.
  • Xanthan gum is commercially available, for example, under the tradename KELTROLTM from Monsanto Performance Materials, a unit of Monsanto Company, St. Louis, MO 63167, USA.
  • topical carbonic anhydrase inhibitors of use in the present invention include those compounds described in U.S. Patent Nos. 4,797,413, 4,386,098, 4,416,890, 4,426,388, 5,378,703, 5,240,923 and 5,153,192; and the like.
  • Preferred topical carbonic anhydrase inhibitors are the class of compounds of the structural formula (I):
  • A is carbon or nitrogen, preferably carbon;
  • Z is -NHR or -OR, preferably -NHR;
  • R is C 1-6 alkyl, either straight or branched chain, preferably C 2-4 alkyl such as ethyl, propyl or isobutyl;
  • X is -S(0) 2 - or -C(O)-, preferably -S(O) 2 -.
  • the carbon atoms to which Z and R 1 are bonded may be chiral.
  • absolute configuration e.g., (R,S) or
  • the first letter represents the chirality the carbon atom to which Z is bonded and the second letter represents the chirality of A when A is carbon.
  • the carbonic anhydrase inhibitors of this invention accordingly may be used as diastereomeric mixtures or single enantiomers or as racemic mixtures.
  • Preferred topical carbonic anhydrase inhibitors for use in the present invention are compounds of formula (I), above, wherein A is carbon; and wherein R is -CH 2 CH 3 and R 1 is -CH 3 ; or R is -CH 2 CH 2 CH 3 and R 1 is -CH 2 CH 2 CH 2 OCH 3 ; or R is -CH 2 CH 3 and R 1 is -CH 2 CH 2 CH 3 ; or R is -CH 2 CH 2 (CH 3 ) 2 and R 1 is hydrogen; or R is -CH 2 CH 3 and R 1 is -CH 2 OCH 2 CH 3 ; and carbons 4 and 6 of the topical carbonic anhydrase inhibitor both have S absolute stereochemical configuration.
  • More preferred carbonic anhydrase inhibitors are dorzolamide, brinzolamide, acetazolamide, metazolamide described in U.S. Patent Nos., 4,797,413, 4,386,098, 4,416,890, 4,426,388, 5,378,703, 5,240,923 and 5,153,192; and the like .
  • Dorzolamide which has recently been approved under the trademark, TRUSOPT®, is the first topically effective CAI for clinical use.
  • Most preferred topical carbonic anhydrase inhibitors are (S,S)-(-)-5,6-dihydro-4-ethylamino-6-methyl-4H-thieno[2,3- b]thiopyran-2-sulphonamide-7,7-dioxide, or an ophthalmologically acceptable salt thereof and 2H-thieno[3,2-e]-l,2-thiazine-6-sulfonamide- 4-(ethylamino)-3,4-dihydro-2-(3-methoxypropyl)-l,l-dioxide or an ophthalmologically acceptable salt thereof.
  • a particularly preferred topical carbonic anhydrase inhibitor is dorzolamide, especially as its hydrochloride salt.
  • the concentration of TCAI in the present invention is about 0.05 to 5% (w/w), usually about 0.5 to 3% (w/w), and is administered once or twice daily, to each affected eye.
  • the novel method of this invention comprises the topical ocular administration of about 0.025 to 5 mg per day, preferably about 0.25 to 3 mg per day, of the topical carbonic anhydrase inhibitor to each eye. 8 As a unit dosage, between 0.025 and 2.5 mg, preferably between 0.25 and 1.5 mg, of the topical carbonic anhydrase inhibitor is applied to each eye.
  • ophthalmic solutions are usually prepared as isotonic solutions using tonicity adjusting agents such as potassium chloride, sodium chloride, mannitol, dextrose and glycerin.
  • An isotonic solution will have a freezing point depression of approximately -0.54°C.
  • Tonicity may also be measured by the osmolality of the solution, an isotonic solution having an osmolality of about 290 milliosmoles per kilogram (mOs/kg).
  • the ophthalmic compositions of the present invention are hypotonic solutions, with a freezing point depression between about -0.28°C and -0.4°C, and preferably between about -0.31°C and -0.37°C.
  • the hypotonicity of the ophthalmic solutions of the present invention is between about 150 and 215 mOs/kg, and preferably between 170 and 200 mOs/kg.
  • a novel method for increasing retinal and optic nerve head blood velocity by topical application of a composition comprising a hypotonic solution of xanthan gum, a therapeutically effective amount of a topical carbonic anhydrase inhibitor and a therapeutically effective amount of a ⁇ -adrenergic receptor blocking agent.
  • Suitable ⁇ -adrenergic receptor blocking agents include betaxolol, bufetolol, carteolol, levobunolol, metipranolol, and timolol, or an ophthalmologically acceptable salt thereof.
  • a particularly preferred ⁇ -adrenergic receptor blocking agent is timolol maleate.
  • compositions preferably comprise about 0.05 to 5% (w/w) of the topical carbonic anhydrase inhibitor, usually about 0.5 to 3% (w/w), and about 0.01 to 1% (w/w) of the ⁇ -adrenergic receptor blocking agent, preferably about 0.1 to 0.5% (w/w) to be administered once or twice a day to each affected eye.
  • a further novel method of this invention comprises the topical ocular administration of about 0.025 to 5 mg per day, preferably about 0.25 to 3 mg per day, of the topical carbonic anhydrase inhibitor and about 0.005 to 1 mg per day, preferably about 0.05 to 0.5 mg per day, of the ⁇ -adrenergic receptor blocking agent to each eye.
  • a unit dosage between 0.005 and 0.5 mg of the ⁇ - adrenergic receptor blocking agent, and preferably between 0.05 and 0.25 mg of the ⁇ -adrenergic receptor blocking agent, is applied to each eye.
  • the pH of the composition ranges from about 5.0 to about 7.5, preferably about 5.5 to about 7.0.
  • Suitable subjects for the administration of the formulation of the present invention include primates, man and other animals, particularly man and domesticated animals such as cats and dogs.
  • the pharmaceutical preparation may contain non-toxic auxiliary substances such as antibacterial components which are non- injurious in use, for example, thimerosal, benzalkonium chloride, methyl and propyl paraben, benzyldodecinium bromide, benzyl alcohol, or phenylethanol; buffering ingredients such as sodium chloride, sodium borate, sodium acetate, sodium citrate, or gluconate buffers; and other conventional ingredients such as sorbitan monolaurate, triethanolamine, polyoxyethylene sorbitan monopalmitylate, ethylenediamine tetraacetic acid, and the like.
  • auxiliary substances such as antibacterial components which are non- injurious in use, for example, thimerosal, benzalkonium chloride, methyl and propyl paraben, benzyldodecinium bromide, benzyl alcohol, or phenylethanol
  • buffering ingredients such as sodium chloride, sodium borate, sodium acetate, sodium citrate,
  • the active compound, sodium chloride and benzalkonium chloride were dissolved in water for injection.
  • the pH of the composition was adjusted to 5.6 by addition of 0.2 N sodium hydroxide solution, and water for injection was added until the weight of composition was equal to 75 parts of the final weight (Example 1 A) or 65 parts of the final weight (Example IB).
  • the composition was sterilised by filtration, and the solution flushed with sterile nitrogen. Then a clarified, steam sterilised concentrate of 2% xanthan gum was added to the solution of drug and the obtained solution was homogenised by stirring.
  • the solution was aseptically subdivided into sterile vials and sealed.
  • the active compound, sodium citrate, benzalkonium chloride and sorbitol are dissolved in water for injection.
  • the pH of the composition is adjusted to pH 5.0 by addition of hydrochloric acid, and water for injection is added until the weight of the composition is equal to 75 parts of the final weight.
  • the composition is sterilised by filtration, flushing with sterile nitrogen. Then a clarified, steam sterilised concentrate of 2% xanthan gum is added to the solution of the drug and the obtained solution is homogenised by stirring.
  • the solution is aseptically subdivided into sterile vials and sealed.
  • the active compound, sodium citrate, benzalkonium chloride and mannitol are dissolved in water for injection.
  • the pH of the composition is adjusted to pH 5.6 by addition of sodium hydroxide, and water for injection is added until the weight of the composition was equal to 75 parts of the final weight.
  • the composition is sterilised by filtration, flushing with sterile nitrogen. Then a clarified, steam sterilised concentrate of 2% xanthan gum is added to the solution of the drug and the obtained solution is homogenised by stirring.
  • the solution is aseptically subdivided into sterile vials and sealed.
  • the active compound, sodium chloride and benzalkonium chloride were dissolved in water for injection.
  • the pH of the composition was adjusted to pH 5.8 by addition of sodium hydroxide, and water for injection was added until the weight of the composition was equal to 65 parts of the final weight.
  • the composition was sterilised by filtration, flushing with sterile nitrogen. Then a clarified, steam sterilised concentrate of 2% xanthan gum was added to the solution of the drug and the obtained solution was homogenised by stirring.
  • the solution was aseptically subdivided into sterile vials and sealed.
  • the active compound, sodium chloride and benzalkonium chloride were dissolved in water for injection.
  • the pH of the composition was adjusted to pH 6.0 by addition of sodium hydroxide, and water for injection was added until the weight of the composition was equal to 65 parts of the final weight.
  • the composition was sterilised by filtration, flushing with sterile nitrogen. Then a clarified, steam sterilised concentrate of 2% xanthan gum was added to the solution of the drug and the obtained solution was homogenised by stirring.
  • the solution was aseptically subdivided into sterile vials and sealed.
  • the active compound, sodium chloride and benzalkonium chloride were dissolved in water for injection.
  • the pH of the composition was adjusted to pH 6.5 by addition of sodium hydroxide, and water for injection was added until the weight of the composition was equal to 65 parts of the final weight.
  • the composition was sterilised by filtration, flushing with sterile nitrogen. Then a clarified, steam sterilised concentrate of 2% xanthan gum was added to the solution of the drug and the obtained solution was homogenised by stirring.
  • the solution was aseptically subdivided into sterile vials and sealed.
  • the active compounds, sodium chloride and benzalkonium chloride are dissolved in water for injection.
  • the pH of the composition is adjusted to pH 5.6 by addition of sodium hydroxide, and water for injection is added until the weight of the composition was equal to 75 parts of the final weight.
  • the composition is sterilised by filtration, flushing with sterile nitrogen. Then a clarified, steam sterilised concentrate of 2% xanthan gum is added to the solution of the drug and the obtained solution is homogenised by stirring.
  • the solution is aseptically subdivided into sterile vials and sealed.
  • Concentrations of 2% dorzolamide(TRUSOPT®) or 2% dorzolamide in hypotonic xanthan gum formulation were measured by HPLC in various fluids and tissues of pigmented rabbit eye at 1, 2, 4 and 8 hours after dosing.
  • the instillation of the 2% dorzolamide in hypotonic xanthan gum formulation resulted in, for example approximately 2.8-fold higher concentration of dorzolamide in the aqueous humor and iris-ciliary body at 2 hours than the 2% dorzolamide .
  • the retinal, choroidal and scleral concentrations were approximately 2.2-fold higher at 2 hours.
  • the concentration of dorzolamide in the red blood cell and plasma were very similar after dosing with either the 2% dorzolamide (TRUSOPT ® ) or 2% dorzolamide in hypotonic xanthan gum formulations. This suggests that the penetration of dorzolamide into the anterior and posterior portions of the eye is enhanced by the instillation of dorzolamide in the hypotonic xanthan gum formulation and is independent of drug concentrations in the blood.

Abstract

On décrit un procédé permettant d'augmenter la vitesse sanguine au niveau de la tête pour la rétine et le nerf optique, ce procédé consistant à appliquer de manière topique sur l'oeil une composition comprenant des inhibiteurs d'anhydrase carbonique et de la gomme de xanthane hypotonique.
PCT/US1998/013038 1997-06-26 1998-06-22 Procede permettant d'optimiser l'etat de sante de la retine et du nerf optique WO1999000133A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
EP98931510A EP1024810A4 (fr) 1997-06-26 1998-06-22 Procede permettant d'optimiser l'etat de sante de la retine et du nerf optique
AU81622/98A AU740874B2 (en) 1997-06-26 1998-06-22 Method for optimizing retinal and optic nerve health
CA002294343A CA2294343A1 (fr) 1997-06-26 1998-06-22 Procede permettant d'optimiser l'etat de sante de la retine et du nerf optique
JP50566199A JP2002506461A (ja) 1997-06-26 1998-06-22 網膜及び視神経の健康の最適化方法

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US5083597P 1997-06-26 1997-06-26
US60/050,835 1997-06-26
GB9800449.2 1998-01-09
GBGB9800449.2A GB9800449D0 (en) 1998-01-09 1998-01-09 Method for optimizing retinal and optic nerve health

Publications (1)

Publication Number Publication Date
WO1999000133A1 true WO1999000133A1 (fr) 1999-01-07

Family

ID=26312917

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1998/013038 WO1999000133A1 (fr) 1997-06-26 1998-06-22 Procede permettant d'optimiser l'etat de sante de la retine et du nerf optique

Country Status (5)

Country Link
EP (1) EP1024810A4 (fr)
JP (1) JP2002506461A (fr)
AU (1) AU740874B2 (fr)
CA (1) CA2294343A1 (fr)
WO (1) WO1999000133A1 (fr)

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999045929A1 (fr) * 1998-03-09 1999-09-16 Alcon Laboratories, Inc. Traitement des oedemes retiniens a l'aide de brinzolamide
US6174524B1 (en) 1999-03-26 2001-01-16 Alcon Laboratories, Inc. Gelling ophthalmic compositions containing xanthan gum
US6261547B1 (en) 1998-04-07 2001-07-17 Alcon Manufacturing, Ltd. Gelling ophthalmic compositions containing xanthan gum
US6331540B1 (en) 1999-11-01 2001-12-18 Alcon Universal Ltd. Pharmaceutical compositions containing a fluoroquinolone antibiotic drug and xanthan gum
US6352978B1 (en) 2000-07-28 2002-03-05 Alcon Universal Ltd. Pharmaceutical compositions containing tobramycin and xanthan gum
WO2002083175A1 (fr) * 2001-04-11 2002-10-24 Senju Pharmaceutical Co., Ltd. Agents ameliorant la fonction visuelle
WO2008075155A2 (fr) 2006-12-15 2008-06-26 Nicox S.A. Dérivés inhibiteurs de l'anhydrase carbonique
US7875271B2 (en) 2006-03-23 2011-01-25 Senju Pharmaceutical Co., Ltd. Ophthalmic composition comprising xanthan gum and glucose
US7939511B2 (en) 2004-09-28 2011-05-10 Senju Pharmaceutical Co., Ltd. Ophthalmic composition containing xanthan gum and amino acid
US7998942B2 (en) 2005-07-11 2011-08-16 Senju Pharamaceutical Co., Ltd. Eye drop preparation comprising xanthan gum and terpenoid

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8222156B2 (en) 2006-12-29 2012-07-17 Lam Research Corporation Method and apparatus for processing a substrate using plasma
JP5305710B2 (ja) * 2008-03-31 2013-10-02 株式会社ニデック ドルゾラミド塩酸塩点眼液

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US5378703A (en) * 1990-04-09 1995-01-03 Alcon Laboratories, Inc. Sulfonamides useful as carbonic anhydrase inhibitors

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IE50901B1 (en) * 1980-03-04 1986-08-06 Merck & Co Inc Ophthalmic compositions of carbonic anhydrase inhibitors for topical application in the treatment of elevated intraocular pressure
CA2064160C (fr) * 1991-03-27 1998-08-11 Paul J. T. Missel Emploi de polysaccharides gelifiants combines a des substrats finement divises a action de vecteur des medicaments, dans des compositions ophthalmiques a usage local
JP2965267B2 (ja) * 1992-02-21 1999-10-18 アルコン ラボラトリーズ，インコーポレイテッド 局所用抗緑内障組成物
AU666957B2 (en) * 1992-08-28 1996-02-29 Alcon Laboratories, Inc. Use of certain anionic surfactants to enhance antimicrobial effectiveness of ophthalmic compositions
US5789435A (en) * 1995-05-22 1998-08-04 Advanced Research And Technology Institute Method to increase retinal and optical nerve head blood flow velocity in order to preserve sight

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US5378703A (en) * 1990-04-09 1995-01-03 Alcon Laboratories, Inc. Sulfonamides useful as carbonic anhydrase inhibitors

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Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999045929A1 (fr) * 1998-03-09 1999-09-16 Alcon Laboratories, Inc. Traitement des oedemes retiniens a l'aide de brinzolamide
US6261547B1 (en) 1998-04-07 2001-07-17 Alcon Manufacturing, Ltd. Gelling ophthalmic compositions containing xanthan gum
US6174524B1 (en) 1999-03-26 2001-01-16 Alcon Laboratories, Inc. Gelling ophthalmic compositions containing xanthan gum
US6331540B1 (en) 1999-11-01 2001-12-18 Alcon Universal Ltd. Pharmaceutical compositions containing a fluoroquinolone antibiotic drug and xanthan gum
US6352978B1 (en) 2000-07-28 2002-03-05 Alcon Universal Ltd. Pharmaceutical compositions containing tobramycin and xanthan gum
US7109208B2 (en) 2001-04-11 2006-09-19 Senju Pharmaceutical Co., Ltd. Visual function disorder improving agents
WO2002083175A1 (fr) * 2001-04-11 2002-10-24 Senju Pharmaceutical Co., Ltd. Agents ameliorant la fonction visuelle
US7696194B2 (en) 2001-04-11 2010-04-13 Senju Pharmaceutical Co., Ltd. Visual function disorder improving agents
US7939511B2 (en) 2004-09-28 2011-05-10 Senju Pharmaceutical Co., Ltd. Ophthalmic composition containing xanthan gum and amino acid
US8450295B2 (en) 2004-09-28 2013-05-28 Senju Pharmaceutical Co., Ltd. Ophthalmic composition containing xanthan gum and amino acid
US7998942B2 (en) 2005-07-11 2011-08-16 Senju Pharamaceutical Co., Ltd. Eye drop preparation comprising xanthan gum and terpenoid
US7875271B2 (en) 2006-03-23 2011-01-25 Senju Pharmaceutical Co., Ltd. Ophthalmic composition comprising xanthan gum and glucose
WO2008075155A2 (fr) 2006-12-15 2008-06-26 Nicox S.A. Dérivés inhibiteurs de l'anhydrase carbonique
WO2008075155A3 (fr) * 2006-12-15 2008-11-06 Nicox Sa Dérivés inhibiteurs de l'anhydrase carbonique

Also Published As

Publication number Publication date
AU740874B2 (en) 2001-11-15
CA2294343A1 (fr) 1999-01-07
JP2002506461A (ja) 2002-02-26
AU8162298A (en) 1999-01-19
EP1024810A1 (fr) 2000-08-09
EP1024810A4 (fr) 2003-06-11

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