Use of cloprostenol and fluprostenol analogues to treat glaucoma and ocular hypertension
AssigneeAlcon Laboratories, Inc.
InventorsPeter G. Klimko, John E. Bishop, Verney L. Sallee, Paul W. Zinke, Tom R. Dean, George E. Barnes, Michael L. Chandler
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Abstract
Disclosed is the use of cloprostenol and fluprostenol analogues and combinations thereof with other medicaments for the treatment of glaucoma and ocular hypertension and ophthalmic compositions therefor. Also disclosed are methods of treating optic nerve disorders using the cloprostenol and fluprostenol analogues.
Claims21
A method of treating glaucoma and ocular hypertension which comprises topically administering to the affected eye a composition comprising a therapeutically effective amount of a combination of a first compound selected from the group consisting of beta-blockers, carbonic anhydrase inhibitors, adrenergic agonists, and cholinergic agonists;
- together with a second compound having the absolute stereochemical structure of the following formula (IV):
- wherein:
- R1=H;
- C1-C12 straight-chain or branched alkyl;
- C1-C12 straight-chain or branched acyl;
- C3-C8 cycloalkyl;
- or a cationic salt moiety;
- R2, R3=H, or C1-C5 straight-chain or branched alkyl;
- or R2 and R3 taken together may represent O;
- X=O, S, or CH2;
- - - - represents any combination of a single bond, or a cis or trans double bond for the alpha (upper) chain;
- and a single bond or trans double bond for the omega (lower) chain;
- R9=H, C1-C10 straight-chain or branched alkyl, or C1-C10 straight-chain or branched acyl;
- R11=H, C1-C10 straight-chain or branched alkyl, or C1-C10 straight-chain or branched acyl;
- Y=O;
- or H and OR15 in either configuration wherein R15=H, C1—C10 straight-chain or branched alkyl, or C1-C10 straight-chain or branched acyl;
- and
- Z=Cl or CF3;
- with the proviso that when R2 and R3 taken together represent O, then R1≠C1-C12 straight-chain or branched acyl;
- and when R2=R3=H, then R1≠a cationic salt moiety.
A topical ophthalmic composition for the treatment of glaucoma and ocular hypertension comprising an ophthalmically acceptable carrier and a therapeutically effective amount of a combination of a first compound selected from the group consisting of beta-blockers, carbonic anhydrase inhibitors, adrenergic agonists, and cholinergic agonists;
- together with a second compound having the absolute stereochemical structure of the following formula (IV) and being substantially free of the enantiomer of said compound:
- wherein:
- R1=H;
- C1-C12 straight-chain or branched alkyl;
- C1-C12 straight-chain or branched acyl;
- C3-C8 cycloalkyl;
- or a cationic salt moiety;
- R2, R3=H, or C1-C5 straight-chain or branched alkyl;
- or R2 and R3 taken together may represent O;
- X=O, S, or CH2;
- - - - represents any combination of a single bond, or a cis or trans double bond for the alpha (upper) chain;
- and a single bond or trans double bond for the omega (lower) chain;
- R9=H, C1-C10 straight-chain or branched alkyl, or C1-C10 straight-chain or branched acyl;
- R11=H, C1-C10 straight-chain or branched alkyl, or C1-C10 straight-chain or branched acyl;
- Y=O;
- or H and OR15 in either configuration wherein R15=H, C1-C10 straight-chain or branched alkyl, or C1-C10 straight-chain or branched acyl;
- and
- Z=Cl or CF3;
- with the proviso that when R2 and R3 taken together represent O, then R1≠C1-C12 straight-chain or branched acyl;
- and when R2=R3=H, then R1≠a cationic salt moiety;
- and
- with the further proviso that the following compound be excluded:
- cyclopentane heptenol-5-cis-2-(3-αhydroxy-4-m-chlorophenoxy-1-trans-butenyl)-3,5 dihydroxy, [1α, 2β, 3α, 5α].
A method of treating an optic nerve disorder, which comprises administering to the affected eye a composition comprising a therapeutically effective amount of a compound having the absolute stereochemical structure of the following formula (IV) an being substantially free of the enantiomer of said compound:
- wherein:
- R1=H;
- C1-C12 straight-chain or branched alkyl;
- C1-C12 straight-chain or branched acyl;
- C3-C8 cycloalkyl;
- or a cationic salt moiety;
- R2, R3=H, or C1-C5 straight-chain or branched alkyl;
- or R2 and R3 taken together may represent O;
- X=O, S, or CH2;
- - - - represents any combination of a single bond, or a cis or trans double bond for the alpha (upper) chain;
- and a single bond or trans double bond for the omega (lower) chain;
- R9=H, C1-C10 straight-chain or branched alkyl, or C1-C10 straight-chain or branched acyl;
- R11=H, C1-C10 straight-chain or branched alkyl, or C1-C10 straight-chain or branched acyl;
- Y=O;
- or H and OR15 in either configuration wherein R15=H, C1-C10 straight-chain or branched alkyl, or C1-C10 straight-chain or branched acyl;
- and
- Z=Cl or CF3;
- with the proviso that when R2 and R3 taken together represent O, then R1≠C1-C12 straight-chain or branched acyl;
- and when R2=R3=H, then R1≠a cationic salt moiety;
- and
- with the further proviso that the following compound be excluded:
- cyclopentane heptenol-5-cis-2-(3-αhydroxy-4-m-chlorophenoxy-1-trans-butenyl)-3,5 dihydroxy, [1α, 2β, 3α, 5α].
Dependencies are inferred from the claim text.