Claims for Patent: 5,889,052

Summary for Patent: 5,889,052

Title:	Use of cloprostenol and fluprostenol analogues to treat glaucoma and ocular hypertension
Abstract:	Disclosed is the use of cloprostenol and fluprostenol analogues for the treatment of glaucoma and ocular hypertension. Also disclosed are ophthalmic compositions comprising said compounds.
Inventor(s):	Peter G. Klimko, John E. Bishop, Verney L. Sallee, Paul W. Zinke
Assignee:	Alcon Research LLC
Application Number:	US08/917,795
Patent Claims:	1. 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 compound having the absolute stereochemical structure of the following formula (IV), and being substantially free of the enantiomer of said compound: ##STR11## wherein: R1 =H; C1 -C12 straight-chain or branched alkyl; C1 -C12 straight-chain or branched acyl; C3 -C3 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 straightchain 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-transbutenyl)-3,5 dihydroxy, 1.sub.α, 2.sub.β, 3.sub.α, 5.sub.α !. 2. The method of claim 1, wherein for the compound (IV):R2, R3 taken together represent O; X=CH2 ; represents a cis double bond for the alpha (upper) chain and a trans double bond for the omega (lower) chain; R9 and R11 =H; and Y=OH in the alpha configuration and H in the beta configuration. 3. The method of claim 2, wherein for the compound (IV): Z=CF3. 4. The method of claim 1, wherein: R2 =R3 =H, or R2 and R3 taken together represent O; X=O or CH2 ; R9 =R11 =H; Y=H and OR15 ; and R15 =H. 5. The method of claim 4, wherein: R1 =H, C1 -C12 straight chain or branched alkyl or cationic salt moiety; and R2 and R3 taken together represent O. 6. The method of claim 5, wherein the compound of formula (IV) is selected from the group consisting of 3-oxacloprostenol, 13,14-dihydrofluprostenol, and their pharmaceutically acceptable esters and salts. 7. The method of claim 4, wherein: R1 =H or C1 -C12 straight chain or branched acyl; and R2 =R3 =H. 8. The method of claim 7, wherein the compound formula (IV) is 13,14dihydrocloprostenol pivaloate. 9. The method of claim 1, wherein between about 0.01 and about 1000 μg/eye of the compound is administered. 10. The method of claim 9, wherein between about 0.1 and about 100 μg/eye of the compound is administered. 11. The method of claim 10, wherein between about 0.1 and about 10 μg/eye of the compound is administered. 12. A topical ophthalmic composition for the treatment of glaucoma and ocular hypertension comprising an ophthalmically acceptable carrier and a therapeutically effective amount of a compound having the absolute stereochemical structure of the following formula (IV), and being substantially free of the enantiomer of said compound: ##STR12## 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-μhydroxy4-m-chlorophenoxy-l1-transbutenyl)-3,5 dihydroxy, 1.sub.α, 2.sub.β, 3.sub.α, 5.sub.α !. 13. The composition of claim 12, wherein for the compound (IV):R2, R3 taken together represent O; X=CH2 ; represents a cis double bond for the alpha (upper) chain and a trans double bond for the omega (lower) chain; R9 and R11 =H; and Y=OH in the alpha configuration and H in the beta configuration. 14. The composition of claim 13, wherein for the compound (IV): Z=CF3. 15. The composition of claim 12, wherein: R2 =R3 =H, or R2 and R3 taken together represent O; X=O or CH2 ; R9 =R11 =H; Y=H and OR15 ; and R15 =H. 16. The composition of claim 15, wherein: R1 =H, C1 -C12 straight chain or branched alkyl, or cationic salt moiety; and R2 and R3 taken together represent O. 17. The composition of claim 16, wherein the compound of formula (IV) is selected from the group consisting of 3-oxacloprostenol, 13,14-dihydrofluprostenol, and their pharmaceutically acceptable esters and salts. 18. The composition of claim 15, wherein: R1 =H or C1 -C12 straight chain or branched acyl; and R2 =R3 =H. 19. The composition of claim 18, wherein the compound of formula (IV) is dihydrocloprostenol pivaloate. 20. The composition of claim 12, wherein the concentration of the compound of formula (IV) is between about 0.0003 and about 0.3 wt %. 21. The composition of claim 20, wherein the concentration of the compound of formula (IV) is between about 0.0003 and about 0.3 wt %. 22. The composition of claim 21, wherein the concentration of the compound of formula (IV) is between about 0.003 and about 0.03 wt %.