Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...
Reexamination Certificate
2000-11-27
2002-05-28
Carr, Deborah D. (Department: 1621)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Radical -xh acid, or anhydride, acid halide or salt thereof...
C514S923000, C554S214000, C560S121000, C562S523000
Reexamination Certificate
active
06395786
ABSTRACT:
TECHNICAL FIELD
The present invention relates to a sleep-inducing preparation comprising a prostaglandin derivative as an effective ingredient.
BACKGROUND ART
Since prostaglandin (hereinafter referred to as “PG”) exhibits various important physiological actions in a trace amount, the syntheses of the derivatives from natural PGs and the biological activities have been investigated with the intention of a practical use as medicines and have been reported in many literatures.
Particularly, PGs have been reported on the various central nervous actions and have been clarified as to the intracerebral content, biosynthesis, metabolic pathway, their intracerebral localizations and changes with growth or aging, and there has been taken an interest in the relation of PGs with sleep and wake. Among them, PGD
2
has been known as an intracerebral humoral factor which controls the occurrence or maintenance of sleep, and it was made clear that the sleep induced by PGD
2
in monkeys is undistinguished from the spontaneous natural sleep in brain wave or behavior (Proc. Natl. Acad. Sci. USA, vol. 85, pp. 4082-4086 (1988)), therefore this compound is expected as a compound having a novel sleep-inducing action.
However, PGD
2
derivatives including PGD
2
are presently unpractical due to the problems concerning the effect and the stability as a drug.
DISCLOSURE OF THE INVENTION
As a result of the extensive studies, the present inventors have found that the prostaglandin derivatives having a triple bond between the 13- and 14-position represented by the following formula (I) have a characteristic sleep-inducing action, and thereby the present invention has been accomplished.
That is, the present invention is directed to a sleep-inducing preparation which comprises as an effective ingredient a prostaglandin derivative represented by Formula (I):
wherein X is a halogen atom, Y is a group represented by (CH
2
)
m
, a cis-vinylene group or a phenylene group, Z is an ethylene group, a trans-vinylene group, OCH
2
or S(O)
n
CH
2
, R
1
is a C
3-10
cycloalkyl group, a C
3-10
cycloalkyl group substituted with C
1-4
alkyl group(s), a C
4-13
cycloalkylalkyl group, a C
5-10
alkyl group, a C
5-10
alkenyl group, a C
5-10
alkynyl group or a bridged cyclic hydrocarbon group, R
2
is a hydrogen atom, a C
1-10
alkyl group or a C
3-10
cycloalkyl group, m is an integer of 1 to 3, and n is 0, 1 or 2, or a pharmaceutically acceptable salt thereof.
Further, the present invention is directed to a sleep-inducing preparation which comprises as an effective ingredient a prostaglandin derivative represented by Formula (I) wherein X is a chlorine atom or a bromine atom, Y is a group represented by (CH
2
)
m
or a cis-vinylene group, Z is an ethylene group, a trans-vinylene group, OCH
2
or S(O)
n
CH
2
, R
1
is a C
3-10
cycloalkyl group or a C
4-13
cycloalkylalkyl group, R
2
is a hydrogen atom or a C
1-10
alkyl group, m is an integer of 1 to 3, and n is 0, 1 or 2, or a pharmaceutically acceptable salt thereof.
Furthermore, the present invention is directed to a sleep-inducing preparation which comprises as an effective ingredient a prostaglandin derivative represented by Formula (I) wherein X is a chlorine atom or a bromine atom, Y is a group represented by (CH
2
)
m
or a cis-vinylene group, Z is OCH
2
, R
1
is a C
3-10
cycloalkyl group or a C
4-13
cycloalkylalkyl group, R
2
is a hydrogen atom or a C
1-10
alkyl group, and m is an integer of 1 to 3, or a pharmaceutically acceptable salt thereof.
Still furthermore, the present invention is directed to a sleep-inducing preparation which comprises as an effective ingredient a prostaglandin derivative represented by Formula (I) wherein X is a chlorine atom or a bromine atom, Y is a group represented by (CH
2
)
m
or a cis-vinylene group, Z is SCH
2
, R
1
is a C
3-10
cycloalkyl group or a C
4-13
cycloalkylalkyl group, R
2
is a hydrogen atom or a C
1-10
alkyl group, and m is an integer of 1 to 3, or a pharmaceutically acceptable salt thereof.
Still furthermore, the present invention is directed to a sleep-inducing preparation which comprises as an effective ingredient a prostaglandin derivative represented by Formula (I) wherein Y is a group represented by (CH
2
)
m
, Z is SCH
2
, R
1
is a C
3-10
cycloalkyl group, R
2
is a hydrogen atom or a C
1-10
alkyl group, and m is an integer of 1 to 3, or a pharmaceutically acceptable salt thereof.
Still furthermore, the present invention is directed to the above-mentioned prostaglandin derivative or the pharmaceutically acceptable salt for use as an ingredient for sleep-inducing preparation.
Still furthermore, the present invention is directed to a method for sleep-inducing comprising administering a pharmaceutically effective amount of the above-mentioned prostaglandin derivative or the pharmaceutically acceptable salt to a human.
In the present invention, the halogen atom refers to a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.
Examples of the C
3-10
cycloalkyl group are a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group and a cycloheptyl group.
Examples of the C
3-10
cycloalkyl group substituted with C
1-4
alkyl group(s) are a methylcyclopropyl group, a methylcyclohexyl group and an ethylcyclohexyl group.
Examples of the C
4-13
cycloalkylalkyl group are a cyclopropylmethyl group, a cyclobutylmethyl group, a cyclopentylmethyl group, a cyclopentylethyl group, a cyclohexylmethyl group, a cyclohexylethyl group and a cycloheptylmethyl group.
The C
5-10
alkyl group refers to a straight or branched alkyl group, and examples thereof are a pentyl group, a hexyl group, a heptyl group, an octyl group, a 1-methylpentyl group, a 2-methylpentyl group, a 1-methylhexyl group, a 2-methylhexyl group, a 2,4-dimethylpentyl group, a 2-ethylpentyl group, a 2-methylheptyl group, a 2-ethylhexyl group, a 2-propylpentyl group, a 2-propylhexyl group and a 2,6-dimethylheptyl group.
The C
5-10
alkenyl group refers to a straight or branched alkenyl group, and examples thereof are a 3-pentenyl group, a 4-hexenyl group, a 5-heptenyl group, a 4-methyl-3-pentenyl group, a 2,4-dimethylpentenyl group, a 6-methyl-5-heptenyl group and a 2,6-dimethyl-5-heptenyl group.
The C
5-10
alkynyl group refers to a straight or branched alkynyl group, and examples thereof are a 3-pentynyl group, a 3-hexynyl group, a 4-hexynyl group, a 1-methylpent-3-ynyl group, a 2-methylpent-3-ynyl group, a 1-methylhex-3-ynyl group and a 2-methylhex-3-ynyl group.
Examples of the bridged cyclic hydrocarbon group are a bornyl group, a norbornyl group, an adamantyl group, a pinanyl group, a thujyl group, a caryl group and a camphanyl group.
The C
1-10
alkyl group for R
2
refers to a straight or branched alkyl group, and examples thereof are a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a tert-butyl group, a pentyl group, an isopentyl group, a 2-ethylpropyl group, a hexyl group, an isohexyl group, a 1-ethylbutyl group, a heptyl group, an isoheptyl group, an octyl group, a nonyl group and a decyl group.
Examples of the pharmaceutically acceptable salt are salts with alkali metal (e.g. sodium or potassium), alkali earth metal (e.g. calcium or magnesium), ammonia, methylamine, dimethylamine, cyclopentylamine, benzylamine, piperidine, monoethanolamine, diethanolamine, monomethylmonoethanolamine, tromethamine, lysine, a tetraalkyl ammonium and tris(hydroxymethyl)aminomethane.
According to the sleep-inducing preparation of the present invention, in view of the sleep-inducing effect, Y is preferably an ethylene group or cis-vinylene group, Z is preferably OCH
2
or SCH
2
, and R
1
is preferably a cycloalkyl group in Formula (I) of the prostaglandin derivatives as the effective ingredient.
Some of the compounds of Formula (I), according to the present invention, are known in WO94/02457, WO94/08959, Japanese Patent Kokai Hei-6-192218, Japanese Patent Kokai Hei-7-242622, Japanese Patent Kokai Hei-7-242623, Japanese Patent Kokai Hei-7-233144, Japanese Patent Kokal Hei-7-28
Kameo Kazuya
Okuyama Shigeru
Ono Naoya
Sato Fumie
Tanami Tohru
Carr Deborah D.
Taisho Pharmaceutical Co. Ltd.
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