Title: Beverage containing caffeine or theobromine and
vinpocetine citrate for stimulating cerebral activity
United States Patent: 6,290,994
Inventors: Lazaro Flores; Consuelo (Madrid, ES); Calvo Lazaro;
Paula (Madrid, ES); Calvo Lazaro; Elena (Madrid, ES); Manresa Ferrero;
Maria Teresa (Madrid, ES); Calvo Mondelo; Fernando (Madrid, ES)
Assignee: Decox, S.L. (Madrid, ES)
Appl. No.: 654332
Filed: September 1, 2000
Foreign Application Priority Data: Apr 12, 1995[ES]
A beverage such as coffee, tea, cocoa or cola soda is described. The
beverage contains caffeine or theobromine and between 0.5 and 30 mg of
vinpocetine citrate per 100 ml of the beverage. The beverage is used to
stimulate cerebral activity.
DESCRIPTION OF THE INVENTION
It has been known for some time that extracts of
decoctions of certain plants such as coffee, tea, cocoa and ginseng, both
that coming from Korea and that coming from Manchuria in their different
species, white or red, such as the so-called Siberian ginseng (Eleoterococcus
senticosus), including the oral administration of the plant itself as
found in nature or ground with some processing, have a characteristic
tonic and stimulating effect which results in a general invigorating of
the physical condition and a parallel stimulating action of mental
activity, which, depending on the plant in question, is more or less
pronounced, on some of the feelings of physical well-being and/or mental
alertness which are produced with a greater and more substantial action
depending on the vegetable species.
The duration and intensity of the stimulating effect on the central
nervous system (CNS) can be obtained, both in the short term and in the
long term, depending on the concentration of the extract or species of
plant used and, in the final analysis, depending on the amount and
combination of active principles which are contained in the plant.
The popular and in some cases medical use of these compounds in their
different forms has been known for many years and there have also been
known certain side effects which at times are undesirable which exist such
as the insomnia produced in certain individuals by coffee, or in a certain
degree of nervousness in some persons who are very sensitive to chocolate.
In each case, these effects are taken into account, which does not prevent
the daily use of these products which have an undeniable popularity
throughout the different areas of the world.
In some countries, coffee is used more in all its varieties, such as
arabica or robusto, while in other countries tea, from green tea in Japan
and China to the innumerable varieties of tea of India or Europe or
Arabia, is used most.
Chocolate and cocoa derivatives are widely used in the Orient as
stimulants of physical and psychic vigor.
There is extensive scientific literature, both chemical as well as
pharmacological and medical, as well as traditional literature, which can
illustrate what has been stated above, but we shall not make reference
thereto due to the great length which such a bibliography would require.
We believe that there is a great need for a composition which can be
administered as a beverage, which has a stimulating effect on the central
nervous system, in particular, stimulating the memory and the cognitive
activity, but which has fewer undesired side effects than those observed
with the customary beverages of daily consumption. In other words,
beverages which can potentiate the stimulating effect, but reduce the
The active ingredients which are responsible for the stimulating effects
have in general been widely identified so that it is known that caffeine
is one of the principal activators of the mental alertness and well-being
produced by coffee or tea, and theobromine is responsible for the effect
of cocoa and derivatives of chocolate.
The action found has been attributed to these xanthic bases, and even
theophylline, which is very closely related to caffeine and theobromine,
is a member of this basic xanthic structure which has closely related
Furthermore, it has been seen that the compounds obtained by synthesis
exhibit a large part of the properties of the natural extracts, the dosing
of their administration being in some cases easier.
The ginsenocides responsible for the invigorating caused by the
administration of ginseng in its various forms and formulations have also
It may even be said that there is a large scientific arsenal which
explains and lists the active principles which are produced by synthesis
or are found in nature, as well as their pharmacological activity.
Furthermore, the properties of the alkaloids of eburnamenine structure are
known for their interesting effects on the cerebral circulation, the
cerebral vascular resistance in the cerebral vessels and their activity of
increasing cerebral metabolism, which can be quantified by the increase in
the consumption of glucose by the nerve cells as well as its greater
resistance to cerebral hypoxia. Among the alkaloids used in therapy which
correspond to this group, we may mention vinpocetine, vincamine,
bromovincamine, eburnamonine or vincamone, among others, which are used
with great success in the treatment of the deterioration of the cognitive
functions in cerebral vascular problems, which arise in general in persons
of advanced age.
The inventors have recently encountered an unexpected result after the
oral administration to healthy volunteers of different ages of these
traditional beverages combined with the compounds of eburnamenine ring
mentioned. This effect has been obtained and optimized by using different
relative concentrations of the components, that is to say by effecting a
gradation of the concentrations of the xanthic bases used and the
eburnamenine ring derivatives in the case of coffee, cocoa or tea, or
dosing the theophylline in the case of its use as component or else dosing
the concentration of the natural ginsenocides or the concentrations of
active principles of Eleteorococus senticosus in the case of the different
ginseng extracts used.
This marked and unexpected powerful synergistic effect is obtained in all
cases with the different concentrations or relative contents used in each
case, and in this way there can be observed a possible adaptation of the
optimum concentration to the individual need measured as response in
mental alertness or in the increase in cognitive capacity or else in the
extent of the reduction or absence of the undesired effects.
Also, by the present invention there can be obtained compositions which
give rise to effects more in the short term or more in the long term, it
being possible, therefore, to use these compositions in the form of
beverages in a rational manner, stimulating the activity and vigor, both
physical and cerebral, in the short, medium or long term, selecting the
optimum effect in accordance with the need and particular sensitivity to
In order to attempt to explain these effects, which seem to result in the
short term and have a duration also in medium and long term, reference has
been had to a number of hypotheses centered generally on the existing
basic knowledge of the biochemistry of the nerve cells.
We will now explain briefly a few facts and possible explanations of this
resultant synergistic phenomenon.
Thus, for example, it is known that vinpocetine increases or inhibits the
formation of phosphodiesterase PDE, as theophylline also does to a lesser
extent. Other xanthines, such as caffeine or theobromine, may also do so.
Adenyl cyclase acts on acid adenosine monophosphate (AMP) producing cyclic
adenosine monophosphate (C-AMP) which, by the action of the PDE, liberates
the AMP again (see French Patent 80 17165, Publication No. 2469180).
Therefore, if theophylline inhibits the action of phosphodiesterase and
therefore inhibits the formation of C-AMP and vinpocetine also does so,
there is an interesting synergistic effect to be considered and used in
order to activate the cerebral activity as a whole. This can be
excellently measured by the methods described in the literature (Biochem.
Biophys. Acta 302:50/1973, etc.) on papillae of animal tissues, for
instance rat brains, and the inhibiting effect of different concentrations
of purified enzyme (PDE) with respect to the C-AMP of the substrate,
determinable quantitatively, can be tabulated and measured perfectly. If
vinpocetine is added to the different solutions of varied concentration of
PDE, it can be seen how it surprisingly acts, showing a clear inhibition
of the enzymatic activity of the PDE on the reference substrate. In
conclusion, this synergism can be used since, due to it, the AMP increases
at the expense of C-AMP, it being possible to have a larger energy
contribution coming from the ATP which is formed due to the greater
availability of non-cyclic AMP, which permits a substantial increase in
the intracellular metabolic processes and, in particular, those of the
neuron cell with the consequent increase in the consumption of glucose and
the placing in operation of the biochemical processes of mobilization of
fats and utilization of the glucose available so as to have a larger
contribution of the energy necessary to accelerate, activate or implement
these processes in which precisely in the brain the energy sources are
made very limited in order that the source of energy coming from the
mobilizable polysaccharides is limited and in any event controlled by a
very precise mechanism for the obtaining of them.
The ATP produced in this way is the source of energy which can be used for
the cerebral biochemistry.
Among other eburnanes, vinpocetine has shown to also increase the levels
of noradrenaline and dopamine in the brain.
We activate precisely the transmitters specifically entrusted with the
cerebral biochemistry and, combining this with the greater obtaining of
cell oxygen contributed by the demonstrated antihypoxic action of
vinpocetine, measurable data can be obtained by experimentation, such as
the measurement of the increase in the cerebral concentration of serotonin
(5HT), released thus as well as a clear increase of its metabolite,
5-hydroxy-indoleacetic acid (5HIAA). This effect is maximum between 2 and
4 hours after administration.
The use of the synergistic mode of the xanthic bases described and an
alkaloid of the eburnane type, for instance, vinpocetine citrate, which
are administered orally, finally causes an increase in the concentration
of neurotransmitters and an increase in ATP, which gives rise to an
effective alteration of the cerebral metabolism which is quantifiable
subjectively and objectively.
We may recall that it has been shown that compounds such as vinpocetine,
theophylline and papaverine inhibit the PDE, while norepinephrine
stimulates the adenyl cyclase, with the consequent effects on the
concentrations of AMP.
It can be said that we obtain parallel phenomena by inhibiting the PDE or
stimulating the function of the adenyl cyclase (ADC) with respect to the
mobilization or immobilization of the AMP in accordance with the scheme:
AMP.fwdarw.C-AMP.fwdarw.AMP and, parallel with this,
These phenomena make it possible to assume that they increase the
consumption of glucose in the brain and that they activate the cerebral
metabolism, as can be determined, thanks to the modern techniques of
cerebral scanning, when applied to persons carrying out given cerebral
functions after the consumption of the beverages which are presented, for
suitable periods of time as compared with the untreated subjects.
Claim 1 of 2 Claims
What is claimed is:
1. A beverage consisting essentially of coffee, tea, cocoa or cola soda
containing caffeine or theobromine and between 0.5 and 30 mg of added
vinpocetine citrate per 100 ml of said beverage.
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