Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2000-10-30
2002-10-01
Dentz, Bernard (Department: 1625)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S473000
Reexamination Certificate
active
06458831
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to the isolation of two compounds namely (−)- Matairesinol (4,4
1
-dihydroxy-3, 3
1
-dimethoxylignan-9, 9
1
-olide) and (−) wikstromol (4,4
1
,8-trihydroxy-3, 3
1
-dimethoxyliganan-9, 9
1
-olide) from the plant source
Cedrus deodara
in significant yields. This invention also identifies the use of the said compounds as an antioxidant or a free radical scavenger.
PRIOR ART
The compound (−)-Matairesinol and (−)-wikstromol as such do not find much commercial value. The structural formulae of (−)-Matairesinol and (−)-wikstromol are as shown in FIG.
1
. Lignans are widely distributed in angiosperms and gymnosperms. The range of their structures and biological activities is broad. Literature indicates that Matairesinol exhibits CAMP phosphodiesterase inhibition activity, [W. Donald Macrae and G. H. Neil Towers,
Biological activities of Lignans
, Phytochemistry 23 (6), 1207-20 (1984)]. (−)-Wikstromol is found to be active against p-388 lymphocyte leukemia and anti-HIV activity (M. K. Kharmlach, R. Dhal and E. Brown, Premieres syntheses totales du (+)-wikstromol, de la (−)-Trachelogenine, De la (−)-Nortrachelogenine et des lignoides apparentes—Tetrahedran 48, 10115-10126 (1992)).
The wood of
Cedrus deodar
possesses diaphoretic, diuretic and carminative properties, and it is useful in treatment of fevers, piles and pulmonary and urinary disorders. The extract of the bark is astringent and useful for fevers, diarrhea and dysentery. The oleoresin of deodar and the dark-colored oil obtained from the wood are valued for their application for ulcers and skin diseases. [Ref: Wealth of India, Vol.II, P.108-10 (1950) (published by CSIR)].
A close look at literature suggests that the lignan, seco-isolariciresinalldiglycoside (SDG) which has been reported to possess multitude of activities is isolated from [U.S. Pat. No. 5,846,944]. The natural lignans (−)-matairesinol reduce the binding of H-labeled 5&agr;-dihydrotestosterone (DHT) to human sex hormone-binding globulin (SHBG). [Matthias Schottnerand Gerhard Spiteller (J. Nat. Prod. 1998, 61, 119-121)]. P. K. Agarwal and R. P. Rastogi (Phytochemistry Vol 21, No 6, pp 1459-1461, 1982) reported isolation of two lignans meso-secoisolariciresinol and cedrusinin from
Cedrus deodara.
The isolation of matariesional in 0.10% yield and (+)-wikstromol in 0.124% yield is reported from
Wikstroemia viridiflora
(Wikstromol, a new lignan from
Wikstroemia viridiflora
—Sheela Tandon and R. P. Rastogi; Phytochemistry 1976, vol 15, pp 1789-1791).
The extraction of the lignans and other constituents namely (−)-nortrachelogenin, carinol and carissanol from
Carissa edulis
has been reported by Hans Achenbach, Reiner Waibel and Ivan Addae-Mensah, Ref. Phytochemistry, Vol. 22, No. 3, pp. 749-753, 1983.
There is a considerable amount of epidemiological evidence indicating an association between diet rich in fruits and vegetables and a decreased risk of cardiovascular disease and certain forms of cancer. It is generally assumed that the active principles contributing to these protective effects are nothing but antioxidant phytochemicals.
Recent research is directed to find out phytochemicals from plant sources in highlighting the role of polyphenolic compounds of plant materials as antioxidants, antimutagenic, anti inflammatory, antiatherosclerotic, antidiabetic, antihepatotoxic and antimicrobial agents. [Overview of flax lignans by Neil D. Westcott and Alister D. Muir, Crop Utilization Section, Saskatoon Research Centre, Agriculture and Agri-Food Canada, 107, Science Place, Saskatoon, SK S7N 0X2, Canada in Volume II—January 2000—inform]. Alcoholic extract of stem
C. deodara
was found to have anti-cancer activity. [Ref. Medicinal Plants of India (ICMR) Vol.I, 1976, pp. 214 and 215].
Medicinal importance of antioxidant active principles are acquiring importance because of the involvement of free radical mediated oxidative stress in age related diseases.
Free radicals are highly energized molecules that contain an unpaired electron. These are produced through normal biological and environmental processes involving oxygen and can trigger chain reactions that product more free radicals. Normally there is a balance between the amount of free radicals generated in the body and antioxidants to protect against them. However, natural antioxidants present in the body can cope up only with the optimal generation of free radicals and any additional burden of free radicals or lack of antioxidant protection can tip this balance and lead to oxidative stress.
There is a need for free radical scavengers or antioxidant principles isolated from natural resources for preparation of formulations useful in alleviating diseases. Hence, it becomes necessary to look for other lignans possessing related and important biological properties.
Accordingly, the applicants conducted a detailed study on principles from
Cedrus deodara
and this investigation led to the isolation of two active principles namely, Matairesinol and wikstromol. These compounds although hitherto isolated from Wikstromia spp. were in low yields.
Cedrus deodara
hence is a new source for these lignans and their presence in this taxon in significantly high yields makes this invention more important.
OBJECTS OF THE INVENTION
The main object of the invention relates to use of (−)-wikstromol and/or (−)-matairesinol as free radical scavengers or antioxidants:
Another object of the invention is to provide methods for the isolation of (−)-wikstromol and/or (−)-matairesinol from
Cedrus deodara.
Still another object of the invention is to provide methods for the treatment of arteriosclerosis.
SUMMARY OF THE INVENTION
Accordingly, the invention provides novel compositions containing (−)-wikstromol and/or (−)-matairesinol and useful as free radical scavengers and antioxidants. The invention further provides methods for the isolation of (−)-wikstromol and/or (−)-matairesinol from
Cedrus deodara
as well as use of the compounds for the treatment of arteriosclerosis.
DETAILED DESCRIPTION
Accordingly, the invention provides a composition comprising an effective amount of (−)-wikstromol together with or associated with an additive and useful as an antioxidant.
In yet another embodiment the composition contains an effective amount of (−)-matairesinol together with additives and useful as an antioxidant.
In another embodiment the additive is selected in such a manner that they has no effect with the active principles of the composition such as nutrients etc., The additive is such that they enhance and do not retard the activity of the active ingredients i.e. (−)-wikstromol and/or (−)-matairesinol.
In another embodiment the additive is selected from nutrients such as carbohydrates, proteins, sugar and pharmaceutically acceptable carriers.
In another embodiment the ratio of (−)-wikstromol and/or (−)-matairesinol with the additive is in the range between 0.1:10 to 2:10.
In an embodiment (−)-wikstromol and/or (−)-Matairesinol present in an amount of 250-300 mg.
Further the invention provides a process for the isolation of (−)-wikstromol and/or (−)-matairesinol from the
Cedrus deodara
, said process comprising the steps of
a) extraction of the pulverized plant parts of
Cedrus deodara
with solvents to remove the essential oils;
b) concentrating the extract under vacuum to obtain a residue;
c) adding ethyl acetate to the residue obtained in step (b);
d) separating the solvents by conventional methods;
e) subjecting the residue to a first elution with about 3% methanol in chloroform to obtain (−)-matairesinol; and
f) subjecting the residue of step (e) to a second elution with about 5% methanol to obtain (−)-wikstromol.
The solvents used in step (a) are hexane and chloroform.
In another embodiment, the plant parts of
Cedrus deodara
suc
Raghavan Kondapuram V.
Rao Janaswamy M.
Srinivas Pullela V.
Tiwari Ashok K.
Yadav Jhillu S.
Birch & Stewart Kolasch & Birch, LLP
Council of Scientific and Industrial Research
Dentz Bernard
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