Drug – bio-affecting and body treating compositions – Plant material or plant extract of undetermined constitution...
Reexamination Certificate
2002-12-03
2004-03-30
Prats, Francisco (Department: 1654)
Drug, bio-affecting and body treating compositions
Plant material or plant extract of undetermined constitution...
C424S773000, C424S774000
Reexamination Certificate
active
06713092
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a composition of the plant Withania Somnifera, and, more particularly to a high purity extract composition with advantageous levels of withanolide glycosides and oligosaccharides, a minimum of polysaccharides, and substantially low levels of free withaferin A and equivalents (withanolide aglycones), which composition provides enhanced cognition-enhancing effects for the user, and an extraction process for obtaining such composition, as well as pharmaceutical, nutritional and personal care use products thereof.
2. Description of the Prior Art
The plant Withania Somnifera Dunn. (Solanaceae), commonly known as Ashwagandha, has been used in herbal formulations of the Ayurvedic or Indian system of medicine to attenuate a cerebral function deficit in the geriatric population, and to augment the faculty of learning and memory to provide a non-specific host defense. These beneficial effects help the organism to ward off stress and act as an adaptogen. Ashwagandha also shows significant protection against pentylene tetrazole—induced seizures in experimental models of epilepsy, indicating its potential utility for treatment of petitmal epilepsy. Ashwagandha administration also produces a decrease in the core body temperature suggesting a reduced Body Metabolic Rate (BMR), enhanced body growth and increased longevity.
Typically, commercially available extracts of Ashwagandha obtained from old roots stock are either completely devoid of sitoindosides, or contain only traces of sitoindosides admixed with large amounts of toxic metabolites of withanolide aglycones, and polysaccharides, and wherein the polyoxygenated withasteroids are degraded during conventional extract procedures.
Accordingly, it is an object of this invention to provide a new and improved Withania Somnifera extract composition, having an enhanced level of withanolide glycosides and oligosaccharides, and minimum amounts of polysaccharides and free withaferin A (aglycone), and an improved extraction process for obtaining such compositions.
SUMMARY OF THE INVENTION
What is described herein is a high purity, substantially water soluble, extract of the Withania Somnifera plant, including its roots and leaves, obtained by a defined extraction procedure, in the form of a stable, free-flowing, light yellow-to-brown herbaceous powder composition, which provides enhanced cognition and augmented learning facility when taken in a dosage of about 100-800 mg/day. The biologically-enhancing composition of the invention includes, by weight, (a) at least 8%, preferably to 25%, of withanolide glycosides and sitoindosides, (b) at least 25%, preferably to 75%, of oligosaccharides, preferably having a mol. wt of <2000, and (c) less than 2%, preferably less than 1% of free withaferin A (aglycone). The high levels of oligosaccharides in the composition further reduces any toxic effect of free withaferin A therein.
Pharmaceutical, nutritional and personal care use formulations thereof also are described.
DETAILED DESCRIPTION OF THE INVENTION
Suitably, the extract composition of the invention is obtained by (a) providing root and leaf stock, in a suitable ratio of each, e.g. 1:1, of a Withania Somnifera plant, preferably which is about 1 to 2 years old, (b) extracting the root and leaf stock substantially immediately at about 60° C. with an aqueous-alcoholic solvent, such as water and methanol, ethanol or isopropyl alcohol, in a suitable ratio, e.g. 1:9, preferably with about 0.1-20% of an additive or
exogenous saccharide
such as dextrin, cane sugar, the plants oligosaccharide, &bgr;-cyclodextrin, and the like, to convert the conjugation of free withananolides in the leaves into desirable bioactive wihanolide glycoside; and to enhance the stability of the extract; (c) concentrating the extract under vacuum, (d) treating the residue with an aprotic organic solvent, e.g. chloroform, ethyl acetate, etc. to remove withanolide aglycones therefrom, (e) vacuum drying the insoluble residue below about 60° C., or spray drying, to provide a dry solid, and (f) pulverizing the solid under controlled temperature and humidity conditions.
The aprotic solvent soluble fraction of the extraction process, e.g. chloroform, which contains mainly cytotoxic withanolide aglycones and other constituents of the plant, which do not contribute to the bioactivity of the Ashwagandha composition, can be discarded, if desired.
The aqueous-alcoholic soluble, chloroform-insoluble residue contains withanolide glycoside and sitoindoside components which are potent bioactive constituents of Ashwagandha.
The resultant extract powder also contains very high levels of oligosaccharides which act as a carrier for the bioactive withanolide glycosides. Specifically, this extract (see Table 1, column 2) contains at least 25%, preferably up to 75%, of oligosaccharides, which enhance the bioactivity of the withanolide glycosides. High molecular weight saccharides which decrease its bioactivity i.e. polysaccharides, are present in only small amounts herein.
The composition of the extract compositions of this invention are summarized in Tables 1 and 2 below.
TABLE 1
Standardized Withania Somnifera Extract Powder
ANALYSIS
SPECIFICATION
RESULTS
Identity (IR)
HPLC - PDA spectrum
Confirms
i) Total withanolide glycoside
≧8%
12.7%
conjugates (By HPLC)
ii) Oligosaccharides
≧25%
36.3%
(By HPTLC)
iii) Free withaferin A and
≦2.0%
1.60%
Equivalents - withanolide
aglycones (By HPLC)
Heavy Metals (as PB)
≦0.002%
Complies
Arsenic (As)
≦0.0002%
Complies
Sulfated Ash
≦8%
Complies
Moisture content
≦5%
3.50%
Microbiological Tests
Total Aerobic plate count
<10
3
/g
2 × 10
2
CFU/gm
Escherichia coli
Absent in 1 g
Ni
Salmonella
Absent in 10 g
Nil
Ratio of withanolide glycoside
75-95 to 25-5
89:11
conjugates and free withaferin
A (aglycones)
Ratio of withanolide glycoside
12-35 to 82-65
26:74
conjugates and
oligosaccharides
Product Description
Appearance
Fine Powder
Color
Brown to brownish green
Odor
Charactistic
Taste
Mild bitter
Water-soluble extractive value
≧80%
TABLE 2
Effect of Additives on Extraction of Withania Somnifera
(Root + Leaf) Extracted with 90% Methanol
Additive
Withanolide
Free
glycosides
Oligosaccharides
Withaferin
(% by w/w)
(% w/w)
(% w/w)
Sample
(By HPLC)
(By HPTLC)
(By HPLC)
Withania
10.12
28.90
1.60
somnifera
(Control)
Withania
8.99
33.63
0.67
somnifera/5%
Withania
oligosaccharides
Withania
11.53
25.90
1.54
somnifera/10%
Withania
oligosaccharides
Withania
10.00
42.10
1.22
somnifera/0.1%
B-cyclodextrin
HPTLC Analysis of Withania Somnifera Extracts
Withanolide glycosides/sitoindosides, the major bioactive constituents of Withania Somnifera, are not readily identifiable in HPTLC chromatographs. However, upon carefully controlled hydrolysis, where they are converted into withanolide aglycones, these components are readily observed in their HPTLC fingerprints. On the basis of such post-hydrolysis findings, the presence and amounts of such withanolides/sitoindoside glycosides in the extract composition of the invention was determined.
Analytical and Chromatographic Conditions:
Plate material:
Silica gel 60F254
Solvent:
n-Butanol/Acetic acid/Water 4/1/2
(b efore hydrolysis)
Chloroform/Methanol 90/10
(after hydrolysis)
Application mode:
Camag linomat IV
Development mode:
Twin Trough chamber
Detection wavelength:
260 nm
The withanolide aglycones are highly susceptible to rearrangement under such acidic conditions.
The extract composition of the invention can be formulated into pharmaceutical, personal care and nutritional use compositions as described in the above-mentioned patent. In addition the compositions herein have particular medicinal activities as follows:
Medicinal Activity
One of the most significant characteristics of the Withania somnifera—oligosaccharides compositions is their capacity to form inclusion complexes in which substrates, e.g. withanolide glycosides (-sitoindosides) and aglycones, are sequestered, by way of (i) van der Waals attraction, (ii) hydrogen bon
Coe Susan D.
Katz Walter
Natreon Inc.
LandOfFree
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