Claims for Patent: 6,458,836

Summary for Patent: 6,458,836

Title:	Treatment of ocular hypertension and glaucoma
Abstract:	Disclosed is treatment of ocular hypertension and glaucoma by long-term therapy with a prostaglandin related compound for eliminating or reducing potential iridic pigmentation. Composition useful for the treatment, and use of the prostaglandin related compound for producing the composition are also disclosed.
Inventor(s):	Ueno; Ryuji (Potomac, MD)
Assignee:	Sucampo, A.G. (Zug, CH)
Application Number:	09/900,021
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 6,458,836
Patent Claims:	1. A process for the long term treatment or prophylactic management of ocular hypertension or glaucoma in a human patient by topical ocular administration of a therapeutically effective amount of a prostaglandin related compound at least once a day for at least six months, the improvement to eliminate or reduce potential pigmentation of the iris of a treated eye occurring by said long-term topical ocular application of a prostaglandin related compound, wherein the compound used has the formula (I) ##STR8## wherein W.sub.1, W.sub.2, and W.sub.3 are carbon or oxygen atoms, L, M and N are hydrogen atom, hydroxy, halogen atom, lower alkyl, lower alkoxy, hydroxy (lower)alkyl, or oxo, wherein at least one of L and M is a group other than hydrogen, and the five-membered ring may have at least one double bond; A is --CH.sub.2 OH, --COCH.sub.2 OH, --COOH or a functional derivative thereof; B is single bond, --CH.sub.2 --, --CH.sub.2 --CH.sub.2 --, --CH.dbd.CH--, --C.ident.C--, --CH.sub.2 --CH.sub.2 --CH.sub.2, --CH.dbd.CH--CH.sub.2, --CH.sub.2 --CH.dbd.CH--, --CH.ident.C--Ch.sub.2 --, or --CH.sub.2 --C.ident.C--; R.sub.1 is a saturated or unsaturated bivalent lower or medium aliphatic hydrocarbon residue, which is unsubstituted or substituted with halogen, an alkyl group, hydroxy, oxo, aryl or heterocyclic group; and Ra is a saturated or unsaturated lower or medium aliphatic hydrocarbon residue, which is unsubstituted or substituted with halogen atom, oxo, hydroxy, lower alkyl, lower alkoxy, lower alkanoyloxy, cyclo(lower)alkyl, cyclo(lower)alkyloxy, aryl, aryloxy, heterodcyclic group or heterocyclic-oxy group; cyclo(lower)alkyl; cyclo(lower)alkyloxy; aryl; aryloxy; heterocyclic group; or hetrocyclic-oxy group. 2. The process of claim 1 wherein the functional derivative of A is salts, ethers, esters or amides. 3. The process of claim 2 wherein the amide of A is represented by the formula --CONR'R", wherein each of R' and R" is hydrogen atom, lower alkyl, aryl, alkyl- or aryl-sulfonyl, lower alkenyl and lower alkynyl. 4. The process of claim 2 wherein the compound used is a 13,14-dihydro-15-keto-20 ethyl PGF.sub.2.alpha. isopropyl ester. 5. The process of claim 2 wherein the compound used is 15-keto latanoprost. 6. The process of claim 2 wherein the compound used is 15-keto-17-phenyl-18,19,20-trinor PGF.sub.2.alpha. N-ethylamide. 7. The process of claim 2 wherein the compound used is 13,14,dihydro-15-keto 17-phenyl-18,1920-trinor PGF.sub.2.alpha. N-ethylamide. 8. The process of claim 2 wherein the compound used is 15-keto-16-(3-trifluoromethyl phenoxy)-17,18,19,20-tetranor PGF.sub.2.alpha. isopropyl ester. 9. The process of claim 2 wherein the compound used is 13,14-dihydro-15-keto-16-(3-trifluoromethyl phenoxy)-17,18,19,20-tetranor PGF.sub.2.alpha. isopropyl ester. 10. The process of claim 1 wherein the compound used is administered twice daily for at least six months. 11. The process of claim 1 wherein the human patient is a Caucasian. 12. the process of claim 1 wherein the compound used contains a 15-keto substituent and an omega chain containing a phenyl ring. 13. A process for the long-term treatment or prophylactic management of ocular hypertension or glaucoma in a human patient by topical ocular administration of a therapeutically effective amount of a prostaglandin related compound at least once a day for at least six months, the improvement to eliminate or reduce potential pigmentation of the iris of a treated eye occurring by said long-term topical ocular application of a prostaglandin related compound, wherein the compound used has the formula (III) ##STR9## wherein W.sub.1, W.sub.2 and W.sub.3 are carbon or oxygen atoms, L, M and N are hydrogen atom, hydroxy, halogen atom, lower alkyl, lower alkoxy, hydroxy(lower)alkyl, or oxo, wherein at least one of L and M is group other than hydrogen, and the five-membered ring may have at least one double bond; A is --CH.sub.2 OH, --COCH.sub.2 OH, --COOH or a functional derivative thereof; B is single bond, --CH.sub.2 --, --CH.sub.2 --CH.sub.2 --, --CH.dbd.CH--, --C.ident.C--, --CH.sub.2 --CH.sub.2 --CH.sub.2 --, --CH.dbd.CH--CH.sub.2 --, --CH.sub.2 --CH.dbd.CH--, --C.ident.C--CH.sub.2 --, or --CH.sub.2 --C.ident.C--; R.sub.1 is a saturated or unsaturated bivalent lower or medium aliphatic hydrocarbon residue, which is unsubstituted or substituted with halogen, an alkyl group, hydroxy, oxo aryl or heterocyclic group; Z is ##STR10## wherein R.sub.4 and R.sub.5 are hydrogen atom, hydroxy, halogen atom, lower alkyl, lower alkoxy or hydroxy(lower)alkyl, wherein R.sub.4 and R.sub.5 are not hydroxy, lower alkoxy and/or hydroxy(lower) alkyl at the same time; and Ra' comprises (1) a saturated or unsaturated C.sub.3 to C.sub.5 straight chain aliphatic hydrocarbon beyond carbon atom number 15 substituted by cyclo (lower) alkyl, cyclo (lower)alkyloxy, aryl, aryloxy, heterocyclic group or heterocyclic-oxy group at its terminus or (2) a saturated or unsaturated at least C.sub.6 straight chain aliphatic hydrocarbon residue beyond carbon atom number 15, which is unsubstituted or substituted with halogen atom, oxo hydroxy, lower alkyl, lower alkoxy, lower alkanoyloxy, cyclo(lower)alkyl, cyclo(lower)alkyloxy, aryl, aryloxy, heterocyclic group or heterocyclic-oxy group. 14. The process of claim 13 wherein the functional derivative of A is salts, ethers, esters or amides. 15. The process of claim 14 wherein the amide of A is represented by the formula --CONR'R", wherein each of R' and R" is hydrogen atom, lower alkyl, aryl, alkyl- or aryl-sulfonyl, lower alkenyl and lower alkynyl. 16. The process of claim 13 wherein the compound used contains a straight chain beyond carbon atom number 15 of at least 6 carbon atoms. 17. The process of claim 16 wherein the compound used is a docosanoid. 18. The process of claim 13 wherein the compound used contains a straight chain beyond carbon atom number 15 of at least 3 carbon atoms substituted by cyclo(lower)alkyl, cyclo(lower) alkyloxy, aryl, aryloxy, heterocyclic group ar heterocyclic-oxy group at the terminus of the omega chain. 19. The process of claim 18 wherein the compound used is substituted by phenyl at the terminus of the omega chain. 20. The process of claim 13 wherein the compound used is administered twice daily for at least six months. 21. The process of claim 13 wherein the human patient is a Caucasin. 22. A process for the long term treatment or prophylactic management of ocular hypertension or glaucoma in a human patient by topical ocular administration in a hyman patient of a therapeutically effective amount of a prostaglandin related compound at least once a day for at least six months, the improvement to eliminate or reduce portential pigmentation of the iris of a treated eye occurring by said long-term topical ocular application of a prostaglandin related compound, wherein the compound used has the formula (IV) ##STR11## wherein W.sub.1, W.sub.2, and W.sub.3 are carbon or oxygen atoms, L, M and N are hydrogen atom, hydroxy, halogen atom, lower alkyl, lower alkoxy, hydroxy(lower) alkyl, or oxo, wherein at least one of L and M is group other than hydrogen, and the five-membered ring may have at least one double bond; R' and R" are selected from the group consisting of hydrogen atom, lower alkyl, aryl, aklyl- or aryl-sulfonyl, lower alkenyl and lower alkynyl; B is single bond, --CH.sub.2 --, --CH.sub.2 --CH.sub.2 --, --CH.dbd.CH--, --CH.dbd.C--, --CH.sub.2 --CH.sub.2 --CH.sub.2 --, --CH.dbd.CH--CH.sub.2 --, --CH.sub.2 CH.dbd.CH--, --C.ident.C--CH.sub.2 --, or --CH.sub.2 --C.ident.C--; R.sub.1 is a saturated or unsaturated bivalent lower or medium aliphatic hydrocarbon residue, which is unsubstituted or substituted with halogen, an alkyl group, hydroxy, oxo, aryl or heterocyclic group; Z is ##STR12## wherein R.sub.4 and R.sub.5 are hydrogen atom, hydroxy, halogen atom, lower alkyl, lower alkoxy or hydroxy(lower)alkyl, wherein R.sub.4 and R.sub.5 are not hydroxy, lower alkoxy and/or hydroxy(lower)alkyl at the same time; and Ra is a saturated or unsaturated lower or medium aliphatic hydrocarbon residue, which is unsubstituted or substituted with halogen atom, oxo, hydroxy, lower alkyl, lower alkoxy, lower alkanoyloxy, cyclo(lower)alkyl, cyclo(lower))alkyloxy, aryl, aryloxy, heterocyclic group or heterocyclic-oxy group; cyclo(lower)alkyl; cyclo(lower)alkyloxy; aryl; aryloxy; heterocyclic group; heterocyclic-oxy group. 23. The process of claim 22 wherein the compound used is 17-phenyl-18,19,20-trinor PGF.sub.2.alpha. N-ethylamide. 24. The process of claim 22 wherein the compound used is administered twice daily for at least six months. 25. The process of claim 24 wherein the human patient is a Caucasian.