Use of 15-keto-prostaglandin compound for improvement of encephalic function

A method of treatment for improving a deterioration of encephalic function caused by a condition comprising or associated with ischemic lesion, hemorrhagic lesion, local or propagated pressure lesion due to edema or hydrocephalia or a disorder of cerebral metabolism secondarily induced by a disorder of cerebral circulation kinetics which comprises administering, to a subject in need of such treatment, a compound of the formula:

• ##STR12## wherein Q.sub.1 is halogen, Q.sub.2 is hydrogen or halogen, E is --CH.sub.2 --CH.sub.2 -- or --CH.dbd.CH--, Ra is hydrogen or lower alkyl, Rb is single bond or lower alkylene, and Rc is lower alkyl which is unsubstituted or substituted with halogen, lower cycloalkyl which is unsubstituted or substituted with lower alkyl, phenyl which is unsubstituted or substituted with halogen or halo(lower)alkyl, or phenoxy which is unsubstituted or substituted with halogen or halo(lower) alkyl or a pharmaceutically acceptable salt in case of Ra is hydrogen, with the proviso that when Rc is phenoxy, Rb is lower alkylene.

A method of inhibiting cerebrovascular contraction which comprises administering, to a subject in need of such treatment, a compound of formula (I) ##STR13## wherein X and Y are hydrogen, hydroxy, halo, lower alkyl, hydroxy(lower)alkyl, or oxo with the proviso that at least one of X and Y is other than hydrogen and the five-membered ring may have at least one double bond, Z is hydrogen or halo, A is --CH.sub.2 OH, --COCH.sub.2 OH, --COOH or a salt, an ester or an amide of --COOH, B is --CH.sub.2 --CH.sub.2 --, --CH.dbd.CH-- or --C.tbd.C--, R.sub.1 is bivalent saturated or unsaturated, lower or medium aliphatic hydrocarbon residue, which is unsubstituted or substituted with halogen, oxo, phenyl, tolyl, xylyl or thienyl, R.sub.2 is saturated or unsaturated, lower or medium aliphatic hydrocarbon residue which is unsubstituted or substituted with halo, hydroxy, oxo, lower alkoxy, lower alkanoyloxy, cyclo(lower)alkyl, aryl or aryloxy and wherein in R.sub.2 aryl and aryl of aryloxy are independently phenyl, tolyl, xylyl or thienyl, in an amount effective for inhibition of cerebrovascular contraction.

A method for improving learning and memory which comprises administering to a subject in need of such improvement a compound of formula (I) ##STR14## wherein X and Y are hydrogen, hydroxy, halo, lower alkyl, hydroxy(lower)alkyl, or oxo with the proviso that at least one of X and Y is other than hydrogen and the five-membered ring may have at least one double bond, Z is hydrogen or halo, A is --CH.sub.2 OH, --COCH.sub.2 OH, --COOH or a salt, an ester or an amide of --COOH, B is --CH.sub.2 --CH.sub.2 --, --CH.dbd.CH-- or --C.tbd.C--, R.sub.1 is bivalent saturated or unsaturated, lower or medium aliphatic hydrocarbon residue, which is unsubstituted or substituted with halogen, oxo, phenyl, tolyl, xylyl or thienyl, R.sub.2 is saturated or unsaturated, lower or medium aliphatic hydrocarbon residue which is unsubstituted or substituted with halo, hydroxy, oxo, lower alkoxy, lower alkanoyloxy, cyclo(lower)alkyl, aryl or aryloxy and wherein in R.sub.2 aryl and aryl of aryloxy are independently phenyl, tolyl, xylyl or thienyl, in an amount effective for improving said learning and memory.

A method of treatment for improving a deterioration of encephalic function caused by ischemia which comprises administering to a subject in need of such treatment, a 15-keto-prostaglandin compound of the formulae (I) or (II) ##STR17## wherein X and Y are hydrogen, hydroxy, halo, lower alkyl, hydroxy(lower)alkyl, or oxo with a proviso that in formula (I) at least one of X and Y is other than hydrogen and the five-membered ring may have at least one double bond, Z is hydrogen or halo, A is --CH.sub.2 OH, --COCH.sub.2 OH, --COOH or a salt, an ester or an amide of --COOH, B is --CH.sub.2 --CH.sub.2 --, --CH.dbd.CH-- or --C.tbd.C--, W is oxygen atom or carbon atom, R.sub.1 is a bivalent saturated or unsaturated, lower or medium aliphatic hydrocarbon residue, which is unsubstituted or substituted with halogen, oxo, phenyl, tolyl, xylyl or thienyl, R.sub.2 is saturated or unsaturated, lower or medium aliphatic hydrocarbon residue which is unsubstituted or substituted with halo, hydroxy, oxo, lower alkoxy, lower alkanoyloxy, cyclo(lower)-alkyl, aryl or aryloxy and wherein in R.sub.2 aryl and aryl of aryloxy are independently phenyl, tolyl, xylyl or thienyl, in an amount effective for improvement of encephalic function.

A method of treatment for improving a deterioration of encephalic function caused by hypoxia which comprises administering to a subject in need of such treatment, a 15-keto-prostaglandin compound of the formulae (I) or (II) ##STR18## wherein X and Y are hydrogen, hydroxy, halo, lower alkyl, hydroxy(lower)alkyl, or oxo with a proviso that in formula (I) at least one of X and Y is other than hydrogen and the five-membered ring may have at least one double bond, Z is hydrogen or halo, A is --CH.sub.2 OH, --COCH.sub.2 OH, --COOH or a salt, an ester or an amide of --COOH, B is --CH.sub.2 --CH.sub.2 --, --CH.dbd.CH-- or --C.tbd.C--, W is oxygen atom or carbon atom, R.sub.1 is a bivalent saturated or unsaturated, lower or medium aliphatic hydrocarbon residue, which is unsubstituted or substituted with halogen, oxo, phenyl, tolyl, xylyl or thienyl, R.sub.2 is saturated or unsaturated, lower or medium aliphatic hydrocarbon residue which is unsubstituted or substituted with halo, hydroxy, oxo, lower alkoxy, lower alkanoyloxy, cyclo(lower)-alkyl, aryl or aryloxy and wherein in R.sub.2 aryl and aryl of aryloxy are independently phenyl, tolyl, xylyl or thienyl, in an amount effective for improvement of encephalic function.

A method of treatment for improving a deterioration of encephalic function caused by hypoxia which comprises administering to a subject in need of such treatment, a compound of the formula (III) ##STR19## wherein Q.sub.1 is halogen, Q.sub.2 is hydrogen or halogen, E is --CH.sub.2 --CH.sub.2 -- or --CH.dbd.CH--, Ra is hydrogen or lower alkyl, Rb is single bond or lower alkylene, and Rc is lower alkyl which is unsubstituted or substituted with halogen, lower cycloalkyl which is unsubstituted or substituted with lower alkyl, phenyl which is unsubstituted or substituted with halogen or halo(lower)alkyl, or phenoxy which is unsubstituted or substituted with halogen or halo(lower)alkyl or a pharmaceutically acceptable salt in case of Ra is hydrogen, with the proviso that when Rc is phenoxy, Rb is lower alkylene, in an amount effective for improvement of encephalic function.