Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
1999-03-22
2001-09-11
Jones, Dwayne C. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C548S512000
Reexamination Certificate
active
06288104
ABSTRACT:
BACKGROUND OF THE INVENTION
This invention relates to the use of mesembrine and related compounds as serotonin-uptake inhibitors, to pharmaceutical compositions comprising as an active ingredient dry material or an extract of a plant of the family Mesembryanthemaceae, standardised as to its active content, and to new compounds.
It is known that the naturally occurring alkaloid mesembrine is useful as a medicament having CNS-stimulating action (see JP71043539 to Tanabe Seiyaku Company Limited).
It is also known that a plant and plant products known colloquially as “kougoed”, “channa” or “kanna” in the Cape of South Africa, are used traditionally by some communities as inebriants, sedatives and to elevate mood. The plants called “kougoed”, “channa” or “kanna” are all members of the family Mesembryanthemaceae, and contains varying amounts of (−)-mesembrine and related alkaloids.
An article entitled Psychoactive constituents of the genus Sceletium N.E.Br. and other Mesembryanthemaceae: a review, by Smith et al, in Journal of Ethnopharmacology, 50 (1996), Pages 119 to 130, reviews the historical data recorded over 300 year period of the use of Sceletium plants in psychoactive preparations, describes techniques for the preparation and use of “kougoed” from plants of Sceletium and documents the subjective experiences of a number of contemporary users. The alkaloid distribution in Sceletium and other members of the family Mesembryanthemaceae are also considered. Chemical studies have indicated as many as nine alkaloids in Sceletium, which fall into three distinct structural categories.
SUMMARY OF THE INVENTION
According to a first aspect of the invention there is provided the use of a compound having the formula I
wherein the ring A is selected from the group consisting of:
R
1
and R
2
are independently selected from H, OH, OCH
3
and O(CH
2
)
n
CH
3
;
R
3
is selected from H, CH
3
and (CH
2
)
n
CH
3
;
n is an integer from 1 to 6;
and Q
1
and Q
2
are independently selected from CH
2
, C═O and CHOH; in the manufacture of a medicament for the treatment of diseases that respond to treatment with a serotonin-uptake inhibitor.
In their role as serotonin-uptake inhibitors, these compounds may be used in the treatment of mild to moderate depression, psychological and psychiatric disorders where anxiety is present, major depressive episodes, ie single episode and recurrent depression with associated anxiety, in alcohol and drug dependence, in the treatment of bulimia nervosa, and in the treatment of obsessive-compulsive disorders.
According to a second aspect of the invention there is provided a pharmaceutical composition in unit dosage form comprising a serotonin-uptake inhibitor having the formula I as set out above, in a dose of from 20 micrograms to 2 milligrams inclusive, preferably in a dose of from 50 micrograms to 500 micrograms inclusive, more preferably in a dose of from 100 micrograms to 300 micrograms inclusive.
According to a third aspect of the invention there is provided a method of treating diseases that respond to treatment with a serotonin-uptake inhibitor comprising administering to a patient in need thereof an effective amount of a compound having the formula I as set out above.
According to a fourth aspect of the invention there is provided a pharmaceutical composition comprising as an active ingredient plant material or an extract of a plant of family Mesembryanthemaceae, containing in each unit dose an amount of from 20 micrograms to 2 milligrams inclusive, preferably from 50 micrograms to 500 micrograms inclusive, more preferably from 100 micrograms to 300 micrograms inclusive, of a compound selected from the group consisting of mesembrine, mesembranol and mesembranone, or a mixture of two or more thereof.
The plant of the family Mesembryanthemaceae is preferably a plant of the genus Sceletium, more preferably a plant of the species Sceletium tortuosum(L.) N.E. Br.
The pharmaceutical composition of the invention is also useful in the treatment of mild to moderate depression, psychological and psychiatric disorders where anxiety is present, major depressive episodes, ie single episode and recurrent depression with associated anxiety, in alcohol and drug dependence, in the treatment of bulimia nervosa, and in the treatment of obsessive-compulsive disorders.
According to a fifth aspect of the invention there is provided a compound having the formula I
wherein the ring A is selected from the group consisting of:
R
1
and R
2
are independently selected from H, OH, OCH
3
and O(CH
2
)
n
CH
3;
R
3
is selected from H, CH
3
and (CH
2
)
n
CH
3
;
n is an integer from 1 to 6;
and Q
1
and Q
2
are independently selected from CH
2
, C═O and CHOH;
with the provisos that:
(1) when the ring A is
R
1
and R
2
are OCH
3
, R
3
is CH
3
, and Q
1
is CH
2
, then Q
2
is not C═O or CHOH;
(2) when the ring A is
R
1
and R
2
are OCH
3
or R
2
is OH and R
2
is H, R
3
is CH
3
, and
Q
1
is CH
2
, then Q
2
is not C═O; and
(3)when the ring A is
R
1
and R
2
are OCH
3
, R
3
is CH
3
, and Q
1
is C═O, then Q
2
is not C═O.
REFERENCES:
patent: 3604112A1 (1987-08-01), None
patent: 46-43538 (1971-12-01), None
patent: 46-43539 (1971-12-01), None
Taguchi et al., “Synthesis of Octahydroindole Derivatives,” Tetrahedrom Letters, 55:5763-5766 (1968).
Jeffs et al., “Total Syntheses of (±)-Joubertinamine, and (±)-N-Demethylmesembrenone,” J. Org. Chem. 48:3861-3863 (1983).
Capps et al., “Sceletium Alkaloids, Part 7.1Structure and Absolute Stereochemistry of (−)-Mesembrane and 3′-Methoxy-4′-O-methyljoubertiamine, Two Minor Bases fromS. NamaquenseL. Bolus: X-Ray Analysis of (−)-Mesembrane Hydrochloride Monohydrate,” J. Chem. Soc. Perkins Trans. 8:1098-1104 (1977).
Langlois et al., “Recherches Dans La Serie Des Aryl-3 Pyrrolidines-II, Syntheses de Produits Apparentes a la Mesembrine et a La Crinine,” Tetrahedron 27:5641-5652 (1971).
Taguchi et al., “Synthesis of Octhydroindole Derivatives,” Chem. Pharm. Bull. 18:1008-1014 (1970).
Kruger et al., “Minor Alkaloids fromSceletium StrictumL. Bol. The Structure of N-Demethylmesembrenol and N-Demthylmesembranol,” Journal of the South African Chemical Institute XXIV:235-237 (1971).
Jeffs et al., “Sceletium Alkaloids. VI. Minor Alkaloids ofS. namaquenseandS. strictum,”J. Org. Chem. 39:2703-2710 (1974).
Pfaffli et al., “Demethylierungen am Mesembrine,” Helvetica Chimica Acta 56:347-355 (1973).
Smith et al., “Psychoactive constituents of the genus Sceletium N.E.Br. and otehr Mesembryanthemaceae: a review,” Journal of Ethnopharmacology 50:119-130 (1996).
Hoshino et al., “Synthesis of Sceletium and Amaryllidaceae Alkaloids, (±)-Mesembrine and (±)-Dihydromaritidine, (±)Epidihydromaritidine, (±-Elwesine, and (±)-Epielwesine1),” Chem. Pharm. Bull. 35:2734-2743 (1987).
Gericke Nigel Peter
Van Wyk Ben-Erik
African Natural Health CC
Clark & Elbing LLP
Delacroix-Muirheid C.
Jones Dwayne C.
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