AU6275999A - Antibiotic compositions for treatment of the eye, ear and nose - Google Patents
Antibiotic compositions for treatment of the eye, ear and nose Download PDFInfo
- Publication number
- AU6275999A AU6275999A AU62759/99A AU6275999A AU6275999A AU 6275999 A AU6275999 A AU 6275999A AU 62759/99 A AU62759/99 A AU 62759/99A AU 6275999 A AU6275999 A AU 6275999A AU 6275999 A AU6275999 A AU 6275999A
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- AU
- Australia
- Prior art keywords
- group
- otic
- ophthalmic
- alkyl
- nasal
- Prior art date
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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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
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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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
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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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
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- 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
- A61K9/0043—Nose
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
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- 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
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- 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
- A61P27/16—Otologicals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
Description
WO 00/18404 PCTIUS99/22625 5 ANTIBIOTIC COMPOSITIONS FOR TREATMENT OF THE EYE, EAR AND NOSE Background of the Invention 10 The present invention is directed to the provision of topical antibiotic pharmaceutical compositions for the treatment of ophthalmic, otic and nasal infections, particularly bacterial infections, and to methods of treating ophthalmic, otic and nasal infections by applying those compositions to the affected tissues. The compositions and 15 methods of the invention are based on the use of a new class of antibiotics. The compositions of the present invention may also contain one or more anti-inflammatory agents. The use of quinolone antibiotics to treat infections represents the current state of 20 the art in the field of ophthalmic pharmaceutical compositions and methods of treatment. For example, a topical ophthalmic composition containing the quinolone ciprofloxacin is marketed by Alcon Laboratories, Inc. under the name CILOXANTM (Ciprofloxacin 0.3%) Ophthalmic Solution. The following quinolones have also been utilized in ophthalmic antibiotic compositions: 25 Ouinolone Product Manufacturer Ofloxacin OCUFLOXTM Allergan Norfloxacin CHIBROXIN TM Merck Lomefloxacin LOMEFLOXTM Senju WO 00/18404 PCTIUS99/22625 The foregoing quinolone antibiotic compositions are generally effective in treating ophthalmic infections, and have distinct advantages over prior ophthalmic antibiotic compositions, particularly those having relatively limited spectrums of antimicrobial 5 activity, such as: neomycin, polymyxin B, gentamicin and tobramycin, which are primarily useful against gram negative pathogens; and bacitracin, gramicidin, and erythromycin, which are primarily active against gram positive pathogens. However, despite the general efficacy of the ophthalmic quinolone therapies currently available, there is a need for improved compositions and methods of treatment based on the use of 10 antibiotics that are more effective than existing antibiotics against key ophthalmic pathogens, and less prone to the development of resistance by those pathogens. There is an even greater need for effective topical compositions and methods for treating otic and nasal infections, particularly bacterial infections. The use of oral 15 antibiotics to treat otic infections in children has limited efficacy, and creates a serious risk of pathogen resistance to the orally administered antibiotics. Ophthalmic, otic and nasal infections are frequently accompanied by inflammation of the infected ophthalmic, otic and nasal tissues and perhaps even surrounding tissues. 20 Similarly, ophthalmic, otic and nasal surgical procedures that create a risk of microbial infections frequently also cause inflammation of the affected tissues. Thus, there is also a need for ophthalmic, otic and nasal pharmaceutical compositions that combine the anti infective activity of one or more antibiotics with the anti-inflammatory activity of one or more steroid or non-steroid agents in a single composition. 25 Summary of the Invention The invention is based on the use of a potent new class of antibiotics to treat ophthalmic, otic and nasal infections, as well as the prophylactic use of these antibiotics 30 following surgery or other trauma to ophthalmic, otic or nasal tissues. The compositions -2- WO 00/18404 PCT/US99/22625 of the present invention may also be administered to the affected tissues during ophthalmic, otic or nasal surgery procedures to prevent or alleviate post-surgical infections. 5 The compositions preferably also contain one or more anti-inflammatory agents to treat inflammation associated with infections of ophthalmic, otic or nasal tissues. The anti-inflammatory component of the compositions is also useful in treating inflammation associated with physical trauma to ophthalmic, otic or nasal tissues, including inflammation resulting from surgical procedures. The compositions of the present 10 invention are therefore particularly useful in treating inflammation associated with trauma to ophthalmic, otic or nasal tissues wherein there is either an infection or a risk of an infection resulting from the trauma. Examples of ophthalmic conditions that may be treated with the compositions of 15 the present invention include conjunctivitis, keratitis, blepharitis, dacyrocystitis, hordeolum and corneal ulcers. The compositions of the invention may also be used prophylactically in connection with various ophthalmic surgical procedures that create a risk of infection. 20 Examples of otic conditions that may be treated with the compostions of the present invention include otitis externa and otitis media. With respect to the treatment of otitis media, the compositions of the present invention are primarily useful in case-s where the tympanic membrane has ruptured or tympanostomy tubes have been implanted. The compositions may also be used to treat infections associated with otic surgical procedures, 25 such as tympanostomy, or to prevent such infections. The compositions of the present invention are specially formulated for topical application to ophthalmic, otic and nasal tissues. The compositions are preferably sterile, and have physical properties (e.g., osmolality and pH) that are specially suited for WO 00/18404 PCT/US99/22625 application to ophthalmic, otic and nasal tissues, including tissues that have been compromised Detailed Description of the Invention 5 The antibiotics used in the compositions and methods of the present invention have the following formula: ( I) R3 0 X COOR R2 N 10 R1 wherein 15 R1 is a cyclopropyl which may be substituted by 1 to 3 of substituents selected from the group consisting of a CI-C 6 alkyl and a halogen atom, a phenyl which may be substituted by 1 to 3 of substituents selected from the group consisting of
CI-C
6 alkoxy, a halogen atom and hydroxy, a C 1
-C
6 alkyl which may be substituted by a halogen atom, a C 2
-C
6 alkanoyloxy or hydroxy, a C 2
-C
6 alkenyl or 20 thienyl; R2 is a member selected from the group consisting of a 1 -piperazinyl group which may have 1 to 3 substituents selected from the group consisting of a C 1
-C
6 alkyl group, a C 1
-C
6 alkanoyl group, a phenyl (CI-C 6 ) alkyl group, and a 2-oxo-1,3 25 dioxolenemethyl group which may be substituted by a phenyl group or a C-C 6 alkyl group; a 1-pyrrolidinyl group which may have 1 to 3 substituents selected -4- WO 00/18404 PCT/US99/22625 from the group consisting of an amino group which can have 1 or 2 substituents selected from a C-C 6 alkyl group and a (C 1
-C
6 )alkooxy-carbonyl group, an amino(C 1
-C
6 )alkyl group which may have 1 to 2 substituents selected from CI-C 6 alkyl group and a (Ci-C 6 )alkoxy-carbonyl group on the amino moiety, and a C 1
-C
6 5 alkyl group; a morpholino group which may have 1 to 3 substituents of CI-C 6 alkyl groups; a 1 -piperidinyl group which may have 1 to 3 substituents selected from the group consisting of a CI-C 6 alkyl group, hydroxy, a halogen atom and oxo group; and a 1,4-diazobicyclo[4.3.0]nonan-4-yl group; 10 R3 is a CI-C 6 alkyl; R is hydrogen atom or a CI-C 6 alkyl; and X is a halogen atom, or a pharmaceutically acceptable salt thereof. 15 The compound Grepafloxacin is most preferred. Grepafloxacin has the following structure:
CH
3 0 20 F COOH N N N 25 Further details regarding the structure, preparation, and physical properties of Grepafloxacin and other compounds of formula (I) are provided in U. S. Patent No. 5,563,138. -5 - WO 00/18404 PCTIUS99/22625 The concentrations of the antibiotics of formula (I) in the compositions of the present invention will vary depending on the intended use of the compositions (e.g., treatment of existing infections or prevention of post-surgical infections), and the relative antimicrobial activity of the specific antibiotic selected. The antimicrobial activity of 5 antibiotics is generally expressed as the minimum concentration required to inhibit the growth of a specified pathogen. This concentration is also referred to as the "minimum inhibitory concentration" or "MIC". The term "MIC90" refers to the minimum concentration of antibiotic required to inhibit the growth of ninety percent (90%) of the strains of a species. The concentration of an antibiotic required to totally kill a specified 10 bacteria is referred to as the "minimum bactericidal concentration" or "MBC". The minimum inhibitory concentration of Grepafloxacin for several bacteria commonly associated with ophthalmic, otic and nasal infections are provided in the following table: Microorganism MIC 90 15 S. aureus/methicillin sensitive 0.13 S. aureus/methicillin resistant 0.13 S. aureus/quinolone resistant 0.13 S. epidermidis/methicillin sensitive 0.13 S. epidermidis/methicillin resistant 0.13 20 S. pneumoniae/penicillin sensitive 0.25 S. pneumoniae/penicillin resistant 0.25 P. aeruginosa 8.0 H. influenzae/-lactamase positive 0.008 H influenzae/plactamase negative 0.008 25 All of the foregoing concentrations are expressed as micrograms per milliliter ("mcg/ml"). The appropriate antibiotic concentration for ophthalmic compositions will generally be an amount of one or more antibiotics of formula (I) sufficient to provide a 30 concentration in the aqueous humor and lacrimal fluid of the eye equal to or greater than -6- WO 00/18404 PCT/US99/22625 the MIC90 level for the selected antibiotic(s), relative to gram-negative and gram-positive organisms commonly associated with ophthalmic infections. The appropriate concentration for otic and nasal compositions will generally be an amount of one or more antibiotics of formula (I) sufficient to provide a concentration in the infected tissues equal 5 to or greater than the MIC90 level for the selected antibiotic(s), relative to gram-negative and gram-positive organisms commonly associated with otic or nasal infections. Such amounts are referred to herein as "an antimicrobial effective amount". The compositions of the present invention will typically contain one or more compounds of formula (I) in a concentration of from about 0.1 to about 1.0 percent by weight ("wt. %") of the 10 compositions. The compositions of the present invention may also contain one or more anti inflammatory agents. The anti-inflammatory agents utilized in the present invention are broadly classified as steroidal or non-steroidal. The preferred steroidal anti-inflammatory 15 agents are glucocorticoids. The preferred glucocorticoids for ophthalmic and otic use include dexamethasone, loteprednol, rimexolone, prednisolone, fluorometholone, and hydrocortisone. The preferred glucocorticoids for nasal use include mometasone, fluticasone, beclomethasone, 20 flunisolide, triamcinolone and budesonide. -7- WO 00/18404 PCT/US99/22625 The dexamethasone derivatives described in U.S. Patent No. 5,223,493 (Boltralik) are also preferred steroidal anti-inflammatory agents, particularly with respect to compositions for treating ophthalmic inflammation. The following compounds are especially preferred: AL-1 529 OajO O AL-2512 OF 5 These compounds are referred to herein as "21-ether derivatives of dexamethasone". The 21-benzyl ether derivative (i.e., compound AL-2512) is particularly preferred. 10 The preferred non-steroidal anti-inflammatory agents are: prostaglandin H synthetase inhibitors (Cox I or Cox II), also referred to as cyclooxygenase type I and type II inhibitors, such as diclofenac, flurbiprofen, ketorolac, suprofen, nepafenac, amfenac, indomethacin, naproxen, ibuprofen, bromfenac, ketoprofen, meclofenamate, piroxicam, sulindac, mefanamic acid, diflusinal, oxaprozin, tolmetin, fenoprofen, benoxaprofen, 15 nabumetome, etodolac, phenylbutazone, aspirin, oxyphenbutazone, NCX-4016, -8- WO 00/18404 PCT/US99/22625 HCT-1026, NCX-284, NCX-456, tenoxicam and carprofen; cyclooxygenase type II selective inhibitors, such as NS-398, vioxx, celecoxib, P54, etodolac, L-804600 and S 33516; PAF antagonists, such as SR-27417, A-137491, ABT-299, apafant, bepafant, minopafant, E-6123, BN-50727, nupafant and modipafant; PDE IV inhibitors, such as 5 ariflo, torbafylline, rolipram, filaminast, piclamilast, cipamfylline, CG-1088, V-11294A, CT-2820, PD-168787, CP-293121, DWP-205297, CP-220629, SH-636, BAY-19-8004, and roflumilast; inhibitors of cytokine production, such as inhibitors of the NFkB transcription factor; or other anti-inflammatory agents known to those skilled in the art. 10 The concentrations of the anti-inflammatory agents contained in the compositions of the present invention will vary based on the agent or agents selected and the type of inflammation being treated. The concentrations will be sufficient to reduce inflammation in the targeted ophthalmic, otic or nasal tissues following topical application of the compositions to those tissues. Such an amount is referred to herein as "an anti 15 inflammatory effective amount". The compositions of the present invention will typically containe one or more anti-inflammatory agents in an amount of from about 0.01 to about 1.0 wt.%. The compositions are typically administered to the affected ophthalmic, otic or 20 nasal tissues by topically applying one to four drops of a sterile solution or suspension, or a comparable amount of an ointment, gel or other solid or semisolid composition, one to four times per day. However, the compositions may also be formulated as irrigating solutions that are applied to the affected ophthalmic, otic or nasal tissues during surgical procedures. 25 The ophthalmic, otic and nasal compositions of the present invention will contain one or more compounds of formula (I) and preferably one or more anti-inflammatory agents, in pharmaceutically acceptable vehicles. The compositions will typically have a pH in the range of 4.5 to 8.0. The ophthalmic compositions must also be formulated to 30 have osmotic values that are compatible with the aqueous humor of the eye and -9- WO 00/18404 PCT/US99/22625 ophthalmic tissues. Such osmotic values will generally be in the range of from about 200 to about 400 milliosmoles per kilogram of water ("mOsm/kg"), but will preferably be about 300 mOsm/kg. 5 Ophthalmic, otic and nasal products are typically packaged in multidose form. Preservatives are thus required to prevent microbial contamination during use. Suitable preservatives include: polyquatemium-1, benzalkonium chloride, thimerosal, chlorobutanol, methyl paraben, propyl paraben, phenylethyl alcohol, edetate disodium, sorbic acid, or other agents known to those skilled in the art. The use of polyquaternium 10 1 as the antimicrobial preservative is preferred. Typically such preservatives are employed at a level of from 0.001% to 1.0% by weight. The solubility of the components of the present compositions may be enhanced by a surfactant or other appropriate co-solvent in the composition. Such co-solvents include polysorbate 20, 60, and 80, polyoxyethylene/polyoxypropylene surfactants (e.g., Pluronic 15 F-68, F-84 and P-103), cyclodextrin, or other agents known to those skilled in the art. Typically such co-solvents are employed at a level of from 0.0 1% to 2% by weight. The use of viscosity enhancing agents to provide the compositions of the invention with viscosities greater than the viscosity of simple aqueous solutions may be desirable to 20 increase absorption of the active compounds by the target tissues or increase the retention time in the eye, ear or nose. Such viscosity building agents include, for example, polyvinyl alcohol, polyvinyl pyrrolidone, methyl cellulose, hydroxy propyl methylcellulose, hydroxyethyl cellulose, carboxymethyl cellulose, hydroxy propyl cellulose or other agents know to those skilled in the art. Such agents are typically 25 employed at a level of from 0.0 1% to 2% by weight. The following examples are provided to further illustrate the ophthalmic, otic and nasal compositions of the present invention. - 10 - WO 00/18404 PCT/US99/22625 Example 1 Ophthalmic/Otic/Nasal Solution Ingredient Amount (wt. %) 5 Grepafloxacin 0.35 Sodium Acetate 0.03 Acetic Acid 0.04 Mannitol 4.60 EDTA 0.05 10 Benzalkonium Chloride 0.006 Water q.s. 100 Example 2 15 Ophthalmic/Otic/Nasal Suspension Ingredient Amount (wt. %) Grepafloxacin 0.3 Dexamethasone, Micronized USP 0.10 20 Benzalkonium Chloride 0.01 Edetate Disodium, USP 0.01 Sodium Chloride, USP 0.3 Sodium Sulfate, USP 1.2 Tyloxapol, USP 0.05 25 Hydroxyethylcellulose 0.25 Sulfuric Acid and/or Sodium Hydroxide, NF q.s. for pH adjustment to 5.5 Purified Water, USP q.s. to 100 30 - 11 - WO 00/18404 PCTIUS99/22625 Example 3 Ophthalmic Ointment Ingredient Amount (wt.%) 5 Grepafloxacin 0.35 Mineral Oil, USP 2.0 White petrolatium, USP q.s 100 1o Example 4 Ophthalmic Ointment Ingredient Amount (wt.%) Grepafloxacin 0.3 15 Fluorometholone Acetate, USP 0.1 Chlorobutanol, Anhydrous, NF 0.5 Mineral Oil,USP 5 White Petrolatum, USP q.s. 100 20 The invention has been described herein by reference to certain preferred embodiments. However, as obvious variations thereon will become apparent to those skilled in the art, the invention is not to be considered as limited thereto. - 12 -
Claims (10)
1. A topical ophthalmic, otic or nasal pharmaceutical composition comprising an antimicrobial effective amount of one or more compounds of the formula: 5 (I) R3 0 X COOR R2 N R1 10 wherein RI is a cyclopropyl which may be substituted by 1 to 3 of substituents selected from the group consisting of a Ci-C 6 alkyl and a halogen atom; a phenyl which 15 may be substituted by 1 to 3 of substituents selected from the group consisting of C 1 -C 6 alkoxy, a halogen atom and hydroxy; a C 1 -C 6 alkyl which may be substituted by a halogen atom, a C 2 -C 6 alkanoyloxy or hydroxy; a C 2 -C 6 alkenyl; or thienyl; 20 R2 is a member selected from the group consisting of a 1 -piperazinyl group which may have 1 to 3 substituents selected from the group consisting of a Ci-C 6 alkyl group, a C 1 -C 6 alkanoyl group, a phenyl (C 1 -C 6 ) alkyl group, and a 2-oxo-1,3 dioxolenemethyl group which may be substituted by a phenyl group or a C 1 -C 6 alkyl group; a 1-pyrrolidinyl group which may have 1 to 3 substituents selected 25 from the group consisting of an amino group which can have 1 or 2 substituents selected from a Ci-C 6 alkyl group and a (CI-C 6 )alkooxy-carbonyl group, an -13 - WO 00/18404 PCTIUS99/22625 amino(Cl-C 6 )alkyl group which may have 1 to 2 substituents selected from C 1 -C 6 alkyl group and a (CI-C 6 )alkoxy-carbonyl group on the amino moiety, and a C1-C6 alkyl group; a morpholino group which may have 1 to 3 substituents C 1 -C 6 alkyl groups; a 1-piperidinyl group which may have 1 to 3 substituents selected from the 5 group consisting of a C 1 -C 6 alkyl group, hydroxy, a halogen atom and oxo group; and a 1,4-diazobicyclo[4.3.0]nonan-4-yl group; R3 is a C 1 -C 6 alkyl; 10 R is hydrogen atom or a CI-C 6 alkyl; and X is a halogen atom, or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable vehicle therefor. 15
2. A topical composition according to Claim 1, wherein the composition further comprises an anti-inflammatory effective amount of a steroidal or non-steroidal anti inflammatory agent. 20
3. A topical composition according to Claim 2, wherein the anti-inflammatory agent comprises a glucocorticoid.
4. A topical composition according to Claim 3, wherein the glucocorticoid is selected from the group consisting of dexamethasone, rimexolone, prednisolone, fluorometholone, 25 hydrocortisone, mometasone, fluticasone, beclomethasone, flunisolide, triamcinolone and budesonide.
5. A topical composition according to Claim 2, wherein the anti-inflammatory agent comprises a non-steroidal agent selected from the group consisting of prostaglandin H 30 synthetase inhibitors, PAF antagonists, and PDE IV inhibitors. - 14 - WO 00/18404 PCTIUS99/22625
6. A topical composition according to Claim 1, wherein the compound of formula (I) comprises grepafloxacin.
7. A topical composition according to Claim 6, wherein the composition further 5 comprises an anti-inflammatory effective amount of a steroidal or non-steroidal anti inflammatory agent.
8. A method of treating or preventing ophthalmic, otic or nasal infections, which comprises topically applying a therapeutically effective amount of the composition of 10 Claim 1 to the affected ophthalmic, otic or nasal tissue.
9. A method of treating or preventing ophthalmic, otic or nasal infections and attendant inflammation, which comprises topically applying a therapeutically effective amount of the composition of Claim 2 to the affected ophthalmic, otic or nasal tissue. 15
10. A method of treating or preventing ophthalmic, otic or nasal infections and attendant inflammation, which comprises topically applying a therapeutically effective amount of the composition of Claim 7 to the affected ophthalmic, otic or nasal tissue. - 15 -
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10251198P | 1998-09-30 | 1998-09-30 | |
US10251098P | 1998-09-30 | 1998-09-30 | |
US60102510 | 1998-09-30 | ||
US60102511 | 1998-09-30 | ||
PCT/US1999/022625 WO2000018404A1 (en) | 1998-09-30 | 1999-09-29 | Antibiotic compositions for treatment of the eye, ear and nose |
Publications (1)
Publication Number | Publication Date |
---|---|
AU6275999A true AU6275999A (en) | 2000-04-17 |
Family
ID=26799456
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
AU62759/99A Abandoned AU6275999A (en) | 1998-09-30 | 1999-09-29 | Antibiotic compositions for treatment of the eye, ear and nose |
Country Status (7)
Country | Link |
---|---|
EP (1) | EP1117406A1 (en) |
JP (1) | JP2002525326A (en) |
AU (1) | AU6275999A (en) |
BR (1) | BR9914158A (en) |
CA (1) | CA2344050A1 (en) |
HK (1) | HK1038692A1 (en) |
WO (1) | WO2000018404A1 (en) |
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AU2005202737B2 (en) * | 1999-12-22 | 2009-01-22 | Bayer Innovation Gmbh | Use of chemotherapeutic agents |
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US6395746B1 (en) | 1998-09-30 | 2002-05-28 | Alcon Manufacturing, Ltd. | Methods of treating ophthalmic, otic and nasal infections and attendant inflammation |
US6716830B2 (en) | 1998-09-30 | 2004-04-06 | Alcon, Inc. | Ophthalmic antibiotic compositions containing moxifloxacin |
US6509327B1 (en) * | 1998-09-30 | 2003-01-21 | Alcon Manufacturing, Ltd. | Compositions and methods for treating otic, ophthalmic and nasal infections |
PT1214056E (en) | 1999-09-24 | 2004-02-27 | Alcon Inc | FORMULATIONS IN TOP SUSPENSION CONTAINING CIPROFLOXACIN AND DEXAMETHASONE |
DE19962470A1 (en) | 1999-12-22 | 2001-07-12 | Schulz Hans Herrmann | Use of chemotherapy drugs |
DE19962353A1 (en) | 1999-12-23 | 2001-07-05 | Henkel Ecolab Gmbh & Co Ohg | Hepatitis A virucide |
US6608078B2 (en) | 2000-05-08 | 2003-08-19 | Wockhardt Limited | Antibacterial chiral 8-(substituted piperidino)-benzo [i,j] quinolizines, processes, compositions and methods of treatment |
CA2412575C (en) | 2000-07-26 | 2009-12-29 | Onkar N. Singh | Improved process for manufacturing compositions containing ciprofloxacin and hydrocortisone |
US7098219B2 (en) | 2000-08-01 | 2006-08-29 | Wockhart Limited | Inhibitors of cellular efflux pumps of microbes |
US6964966B2 (en) | 2001-04-25 | 2005-11-15 | Wockhardt Limited | Generation triple-targeting, chiral, broad-spectrum antimicrobial 7-substituted piperidino-quinolone carboxylic acid derivatives, their preparation, compositions and use as medicaments |
US6878713B2 (en) | 2001-04-25 | 2005-04-12 | Wockhardt Limited | Generation triple-targeting, chiral, broad-spectrum antimicrobial 7-substituted piperidino-quinolone carboxylic acid derivatives, their preparation, compositions and use as medicaments |
DE60208216T2 (en) | 2001-09-21 | 2006-06-29 | Alcon Inc. | METHOD FOR THE TREATMENT OF MEDIUM EARINFECTIONS |
JP2005511743A (en) * | 2001-12-13 | 2005-04-28 | ウォックハート・リミテッド | A new generation of triple-targeted chiral broad-spectrum antibacterial 7-substituted piperidino-quinolone carboxylic acid derivatives, methods for their preparation, compositions, and pharmaceutical use |
US6664267B1 (en) | 2002-05-28 | 2003-12-16 | Wockhardt Limited | Crystalline fluoroquinolone arginine salt form |
US20040175383A1 (en) * | 2002-12-06 | 2004-09-09 | Barr Philip J. | Methods and compositions for treatment of otitis media |
US7164023B2 (en) | 2003-09-04 | 2007-01-16 | Wockhardt Limited | Benzoquinolizine-2-carboxylic acid arginine salt tetrahydrate |
US20090042936A1 (en) * | 2007-08-10 | 2009-02-12 | Ward Keith W | Compositions and Methods for Treating or Controlling Anterior-Segment Inflammation |
US20140219949A1 (en) * | 2011-06-22 | 2014-08-07 | Jiangsu Deda Pharmaceuticals Co. Ltd | Pharmaceutical compositions comprising iodine and steroid and uses thereof for sinus diseases |
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US4551456A (en) * | 1983-11-14 | 1985-11-05 | Merck & Co., Inc. | Ophthalmic use of norfloxacin and related antibiotics |
JP2549285B2 (en) * | 1987-02-02 | 1996-10-30 | 第一製薬株式会社 | Nasal spray |
US5591744A (en) * | 1987-04-16 | 1997-01-07 | Otsuka Pharmaceutical Company, Limited | Benzoheterocyclic compounds |
AU4201189A (en) * | 1988-08-26 | 1990-03-23 | Alcon Laboratories, Inc. | Combination of quinolone antibiotics and steroids for topical ophthalmic use |
DE69620136T2 (en) * | 1995-06-06 | 2002-08-01 | Bayer Ag | ANTIBACTERIAL PREPARATIONS FOR THE EARS WITHOUT IRRITATING, SENSITIZING AND OTOTOXIC EFFECTS |
JPH10130148A (en) * | 1996-09-04 | 1998-05-19 | Senju Pharmaceut Co Ltd | Composition for nebulizer |
-
1999
- 1999-09-29 AU AU62759/99A patent/AU6275999A/en not_active Abandoned
- 1999-09-29 BR BR9914158-2A patent/BR9914158A/en not_active IP Right Cessation
- 1999-09-29 JP JP2000571922A patent/JP2002525326A/en active Pending
- 1999-09-29 WO PCT/US1999/022625 patent/WO2000018404A1/en not_active Application Discontinuation
- 1999-09-29 EP EP99950008A patent/EP1117406A1/en not_active Withdrawn
- 1999-09-29 CA CA002344050A patent/CA2344050A1/en not_active Abandoned
-
2002
- 2002-01-02 HK HK02100004.2A patent/HK1038692A1/en unknown
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2005202737B2 (en) * | 1999-12-22 | 2009-01-22 | Bayer Innovation Gmbh | Use of chemotherapeutic agents |
Also Published As
Publication number | Publication date |
---|---|
BR9914158A (en) | 2001-06-26 |
WO2000018404A1 (en) | 2000-04-06 |
HK1038692A1 (en) | 2002-03-28 |
CA2344050A1 (en) | 2000-04-06 |
EP1117406A1 (en) | 2001-07-25 |
JP2002525326A (en) | 2002-08-13 |
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Legal Events
Date | Code | Title | Description |
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MK5 | Application lapsed section 142(2)(e) - patent request and compl. specification not accepted |