Drug – bio-affecting and body treating compositions – Plant material or plant extract of undetermined constitution...
Reexamination Certificate
2000-06-20
2001-10-23
Weber, Jon P. (Department: 1651)
Drug, bio-affecting and body treating compositions
Plant material or plant extract of undetermined constitution...
Reexamination Certificate
active
06306443
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a method of increasing the concentrations of caffeic acid derivatives and alkylamides and compositions containing the same. In particular, the present invention relates to a method for increasing the concentrations of cichoric acid and dodeca-2E, 4E, 8Z, 10E/Z-tetraenoic acid isobutylamide (“tetraene alkylamides”), which are key active phytochemicals in Echinacea, and raw materials containing the same.
BACKGROUND OF THE INVENTION
In recent years, Echinacea has become one of the most popular commercial medicinal herbs in the world (Wills and Stuart,
Alkylamide and Cichoric Acid Levels in Echinacea purpurea Grown in Australia, Food Chemistry,
67, 385-388 (1999)). Echinacea has received international attention because of its immunostimulatory and other beneficial effects. Although several phytochemicals in Echinacea work together in providing these beneficial effects, caffeic acid derivatives, most notably cichoric acid, and lipophilic alkylamides are indicated as making considerable contributions to Echinaces's immunostimulatory activity (Bauer, R. and Wagner, H.,
Echinacea Species as Potential Immunostimulatory Drugs, Econ. Medic. Plant Res.,
5, 253-321, Wagner, H. and Farnsworth, N. R. (Editors), Academic Press Ltd., New York, N.Y. (1991)).
Echinacea is the genus name for nine herbaceous perennial species native to North America. Echinacea, however, usually refers to
Echinacea angustifolia
,
Echinacea purpurea
, or
Echinacea pallida
. Echinacea was first widely used by several North American Indian tribes against various conditions such as wounds, burns, insect bites, headaches, stomach cramps, coughs, and the measles. The primary use of Echinacea is for increasing resistance to infections in the upper respiratory tract and colds in the upper respiratory tract (Bauer, R. and Wagner, H.,
Echinacea Species as Potential Immunostimulatory Drugs, Econ. Medic. Plant Res.,
5, 253-321, Wagner, H. and Farnsworth, N. R. (Editors), Academic Press Ltd., New York, N.Y. (1991)). Echinacea has anti-inflammatory and antibacterial activities useful in treating conditions such as skin inflammations and urinary tract infections. It has been indicated that Echinacea also fights cancer by stimulation of key lymphocye production, which triggers natural killer cells to destroy tumor cells (see Lersch, C. et al.,
Nonspecific Immunostimulation with Low Doses of Cyclophosphamide, Thymostimulin, and Echinacea purpurea extracts (Echinacin) in Patients with Far Advanced Colorectal Cancer, Cancer Invest.
10(5): 343-348 (1992)).
Cichoric acid, which is a caffeic acid derivative, and tetraene alkylamides are two types of phytochemicals present in Echinacea that are thought to be primarily responsible for Echinacea's beneficial activity. Cichoric acid, in particular, has been noted to inhibit HIV-1 integrase and replication in tissue culture (Robinson, W. et. al.,
Inhibitor of HIV-
1
Replication that Inhibit HIV Integrase, Proc. Natl. Acad. Sci. USA,
93, 6326-6331 (1996)).
The chemical structure of cichoric acid and tetraene alkylamides are shown below:
Other non-limiting examples of caffeic acid derivatives are echinacoside, verbascoside, chlorogenic acid, isocholorogenic acids, cynarine, and caftaric acid, as shown below.
R
1
R
2
R
3
R
4
R
5
R
6
2-O-Caffeoyl-tartaric acid (Caftaric acid)
H
H
OH
H
—
—
2,3-O(Di-caffeoyl-tartaric acid (Cichoric acid)
H
R′
OH
H
OH
H
2,3-O-Di-caffeoyl-tartaric acid-methylester
CH
3
R′
OH
H
OH
H
2-O-Feruloyl-tartaric acid
H
H
OCH
3
H
—
—
2-O-Caffeoyl-3-O-coumaroyl-tartaric acid
H
R′
H
H
H
H
2-O-Caffeoyl-3-O-teruloyl-tartaric acid
H
R′
OH
H
OCH
3
H
2,3-O-Di(5-[&agr;-carboxy-&bgr;-(3,4-di-hydroxy-phenyl)-ethyl)-
H
R′
OH
R′
OH
R′
caffeoyl]-tartaric acid
2-O-Caffeoyl-3-O-(5-[&agr;-carboxy-&bgr;-(3,4-dihydroxy-phenyl)-
H
R′
OH
H
OH
R′
ethyl)-caffeoyl]-tartaric acid
R
R′
Echinacoside
Gluocse (1,8-)
Rhamnose (1,3-)
6-O-Caffeoyl-echinacoside
6-O-Caffeoyl-glucose (1,6-)
Rhamnose (1,3-)
Verbascoside
H
Rhamnose (1,3-)
Dirhamnosyl-verbascoside
H
H
R
1
R
2
R
3
R
4
3-O-Caffeoyl-quinic acid (Chlorogenic acid)
H
R
H
H
Isochlorogenic acids
H
R
R
H
H
R
H
R
H
H
R
R
Cynarine
R
H
H
R
Other non-limiting examples of alkylamides in the roots of
E. purpurea
and
E. angustifolia
are shown below:
It is believed that the root portions of
E. purpurea
provide the highest concentration of alkylamides. The concentration of caffeic acid derivatives are believed to be similar in root and aerial samples. Nonetheless, the concentrations of caffeic acid derivatives and alkylamides may vary from one species of Echinacea to another and may also vary within the same species. The variation of caffeic acid derivatives and alkylamides concentrations within the same species are believed to be partly due to environmental factors, such as the difference in daylight and seasonal change in rainfall.
In the past, to obtain increased amounts of caffeic acid derivatives and alkylamides, one had to grow and harvest more Echinacea plants. Thus, the number of plants having caffeic acid derivatives and alkylamides determined the amount of these phytochemicals available for use in dietary supplements or in other compositions. As a result, more money, time, and effort were involved in producing a commercial product containing these phytochemicals. Therefore, there remains a need to provide a method of increasing the concentrations of caffeic acid derivatives and alkylamides per gram of plant material or, alternatively, a method of making a raw plant material that has increased concentrations of these phytochemicals per gram of plant material. There also remains a need for a composition having increased concentrations of caffeic acid derivatives, such as cichoric acid, and alkylamides, such as tetraene alkylamides, in dietary supplements because of their immunostimulatory and other beneficial effects. The present invention meets the foregoing needs by providing a simple, cost effective method of increasing the concentrations of caffeic acid derivatives (i.e. cichoric acid) and alkylamides (i.e. tetraene alkylamides) in Echinacea and other plants having these phytochemicals as well as compositions containing the same.
SUMMARY OF THE INVENTION
According to the present invention, the foregoing and other objects and advantages are attained by providing a method that involves harvesting a plant having caffeic acid derivatives and alkylamides; separating the plant into fragments; and storing the separated plant fragments in refrigerated conditions at a controlled relative humidity which prevents wilting and microbial decay. The harvesting, separating, and storing steps are collectively referred to as “handling protocol”.
The storage process is a surprising aspect of the present invention because it is generally known by those in the plant industry that phytochemicals with medicinal properties are unstable and will degrade overtime. Thus, storing the presumably unstable plant material to achieve higher concentrations of certain phytochemicals would have been illogical.
In accordance with one aspect of the invention, the plant fragments should be stored at the foregoing temperature and humidity conditions for about 24 hours before the fragments are further processed to obtain the greatest increase in alkylamide levels. In accordance with another aspect of the invention, the plant fragments are stored under the above temperature and humidity conditions for about 96 hours, rather than about 24 hours, to obtain the greatest increase in caffeic acid derivatives. However, storage for about 96 hours can comprise the concentration of alkylamides with generally begins to fall after 24 hours of storage.
Accordingly, it is one object of the invention to obtain increased concentrations of caffeic acid derivatives and alkylamides per plant without having to increase the growth and harvest of plants having these phytochemicals. Because this invention allows for a simple method of
Brovelli Ernesto A.
Johnson Rodney
Ahn Amy I.
Amway Corporation
Patten Patricia A.
Weber Jon P.
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