Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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"SPHAERANTHUS INDICUS DERIVED INGREDIENTS AND THEIR COMPOSITIONS
FOR ENHANCING PHYSICAL PERFORMANCE AND ENERGY LEVELS"
FIELD OF INVENTION:
The invention discloses a herbal ingredient selected from extracts and
fractions standardized to at least one
frullanolide/eudesmanoid sesquiterpene compound(s) derived from Sphaeranthus
indicus or their
composition(s) as natural energy enhancer to provide an onset and steady
maintenance of energy and
mental alertness in a mammal.
The invention further relates to food ingredient formulations such as
beverages, dietary ingredient
formulation, snacks and energy drinks containing the above said herbal
ingredient or its composition(s) for
onset and steady maintenance of energy and mental alertness such as enhancing
physical activity, physical
fitness, mental alertness, energy levels, stamina levels, circulatory health,
blood vessel health or for better
physical and mental health.
BACK GROUND OF THE INVENTION:
Physical activity, such as exercise, particularly in the heat, places a demand
on the body's carbohydrate
stores, such as muscle glycogen, liver glycogen, and plasma glucose. Loss of
water, redistribution and loss
of electrolytes, and the depletion of endogenous carbohydrate reserves are
primary causes of
fatigue/tiredness that impairs one's work capacity. To maintain the body's
physical capabilities, it is
essential that water, electrolytes, carbohydrate, and other nutrients be
provided in a timely and appropriate
manner. Fluid replacement during physical activity has been shown to be
effective in preventing
dehydration and hyperthermia.
The basic force and condition behind all activities of human life is the
presence of energy. Energy is the
vital principle needed to sustain life and it is required for every aspect of
existence - every act uses energy -
thinking, feeling, walking, eating, drinking, dreaming, breathing etc. Energy
is felt and experienced upon
its expenditure. The energy we experience immediately after eating (such as
sweets), or the hype we get
following the consumption of coffee is from the expenditure of energy from
body's energy reserves, not
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through its accumulation. Age, fatigue and stress make people feel deficient
in energy.
This drag in energy very often compromises body's mental alertness. Addressing
body's
energy demands properly, will increase one's efficiency at work place and in
personal
management.
Dietary supplements are used by physically active people or weak people to
increase their
physical performance, physical fitness, improve their health, or reduce the
potentially
negative consequences of physical activity such as injury and chronic fatigue,
or
suppressed immune function.
Many energy beverages, supplements and food ingredient formulations are
presently
available in the market. However, these are fully loaded with disaccharides,
carbohydrate
complexes, proteins, amino acids and vitamins along with numerous other
agents. Many
of these formulations act too quickly to give rise instant energy and not
maintained over
sustained period of time. Besides, these formulations tend to increase the
blood glucose
levels sharply and this is followed by their rapid depletion. This might some
times lead to
complications. Natural supplements, which improve the feeling of being
energetic,
general agility, endurance and mental alertness are thus in great demand.
Studies are in
process in many research groups across the globe to develop a superior product
to address
the above requirements.
Therefore, the present invention addresses the existing need in the art by
providing an
ingredient(s) or composition(s) that provides energy and/or mental alertness.
Thus, the
present invention provides ingredient(s) and/or composition(s) capable of
increasing
energy levels for an extended period of time in a mammal to enhance both
energy levels
and mental alertness and thus solves these needs.
SUMMARY OF INVENTION:
In a major embodiment, the invention discloses a herbal ingredient selected
from extracts
and fractions standardized to at least one fnillanolide/eudesmanoid
sesquiterpene
compound(s) derived from Sphaeranthus indicus or their composition(s) for
onset and
steady maintenance of energy and mental alertness. The sphaeranthus derived
ingredient
and its compositions are useful for enhancing physical activity, physical
fitness, mental
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alertness, energy levels, stamina levels, circulatory health, blood vessel
health or for
better physical and mental health in a mammal.
In another embodiment, the invention relates to the preparation of dietary
supplements,
food ingredient formulations such as beverages, snacks and energy drinks
containing the
above said ingredient(s) or its composition(s) for onset and steady
maintenance of energy
and mental alertness. The formulation is useful for enhancing physical
activity, physical
fitness, mental alertness, energy levels, stamina levels, circulatory health,
blood vessel
health or for better physical and mental health in a mammal.
In a further embodiment, the extracts or fractions are standardized to 7-
hydroxyfrullanolide, its analogs or their compositions for onset and steady
maintenance
of energy; mental alertness and for enhancing physical activity, physical
fitness, mental
alertness, energy levels, stamina levels, circulatory health, blood vessel
health or for
better mental health in warm blooded animals in need thereof.
In yet another embodiment, the invention provides compositions described above
comprise at least one herbal ingredient selected from extract or fraction
standardized to at
least one frullanolide/eudesmanoid sesquiterpene compound(s) derived from
Sphaeranthus indicus in combination with at least one ingredient selected from
extract(s),
fraction(s), active compound(s), phytochemical(s), derived from plant(s),
animal(s) or
microorganisms with proven therapeutic health benefits; pharmaceutically or
dietetically
acceptable agents, active ingredients, vitamins, amino acids and minerals.
In still another embodiment, one or more herbal ingredients derived from
Sphaeranthus
indicus or their compositions are useful for onset and steady maintenance of
energy;
mental alertness and for enhancing physical activity, physical fitness, mental
alertness,
energy levels, stamina levels, circulatory health, blood vessel health or for
better mental
health in warm blooded animals in need thereof.
In another embodiment, the invention provides a method of increasing natural
energy to
provide an onset and steady maintenance of energy and mental alertness in a
mammal,
wherein the method comprises supplementing or treating the said mammal with at
least
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one herbal ingredient selected from the extracts, fractions, compounds;
extracts or
fractions standardized to active compounds derived from Sphaeranthus indicus
or their
compositions.
An embodiment comprises a composition for use in maintaining energy in a warm
blooded animal or mammal, said composition being formulated for oral
administration,
said composition comprising: at least one of a Sphaeranthus indicus component
selected from the group consisting of: a) a Sphaeranthus indicus component,
comprising at least one extract of Sphaeranthus indicus obtained by extraction
with an
organic solvent, alone or in combination with water, said extract of
Sphaeranthus
indicus containing from 5% to 21% 7-hydroxyfrullanolide; and b) a Sphaeranthus
indicus component comprising at least one extract of Sphaeranthus indicus
obtained
by extraction with a solvent selected from the group consisting of Cl to 05
alcohols,
and mixtures thereof, said extract containing at least one frullanolide or
eudesmanoid
sesquiterpene compound; in admixture with a suitable excipient, diluent, or
carrier.
BRIEF DESCRIPTION OF FIGURES:
Figure I: Figure shows Energy endurance capacity of LI12508 on swimming
parameters.
The bars represent resting time, moving slow time and moving fast times in
seconds.
Values are expressed as Mean S.E.M, n=6. * p<0.05 and ** p<0.01 as compared
to
Control (ANOVA followed by Tukey's test)
Figure II: Figure shows Percentage of energy endurance capacity of LI12508.
The bars
represent percentage resting time, moving slow time and moving fast times in
seconds.
Figure III: Figure shows Energy endurance capacity-Average distance travelled
in mm.
The bars represent average travelled by the control group and treatment group
of animals
supplemented with 100 mg/kg or 250 mg/kg body weight. Values are expressed as
Mean
S.E.M, n=6. ** p<0.01 as compared to Control (ANOVA followed by Tukey's test.
Figure IV: Figure shows Energy Endurance capacity. The bars represent Average
velocity exhibited by the control group and treatment group (100 mg/kg or 250
mg/kg
body weight) of animals. Values are expressed as Mean S.E.M, n=6. * p<0.05
as
compared to Control (ANOVA followed by Tukey's test).
Date Recue/Date Received 2020-04-09
4a
DETAILED DESCRIPTION OF INVENTION:
For the purpose of this invention, the phrase 'herbal ingredient' OR 'herbal
ingredients'
OR 'said herbal ingredients' used in the specification and claims of the
present invention
refer to the extract(s), fraction(s); extract(s) or fraction(s) standardized
to at least one
frullanolide/eudesmanoid sesquiterpene compound(s) derived from Sphaeranthus
indicus
or their composition(s). The phrase 'herbal ingredient' OR 'herbal
ingredients' is used
interchangeably through out the specification and the same may be appreciated
as such by
the person skilled in the art.
Date Recue/Date Received 2020-04-09
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The word 'composition' OR 'compositions' OR 'mixture' OR 'mixtures' determine
the
combination of one or more ingredients selected from extract(s), fraction(s)
or
compound(s) derived from Sphaeranthus indicus or other biologically active
ingredients.
The phrase 'biologically active ingredient' or 'biologically active
ingredients' refers to
other component(s) used for making compositions and selected from extract(s),
fraction(s), active compound(s), phytochemical(s); powder(s) derived from
plant(s),
animal(s) or microorganisms with proven therapeutic health benefits;
pharmaceutically or
dietetically acceptable active ingredients, vitamins, amino acids or minerals.
The phrase 'weak people' means those individuals who may or may not be
suffering from
a disease and the weakness can be of physical or mental.
The word 'subject' OR 'subjects' means warm blooded animals, cold blooded
animals,
birds, horses, human beings or mammals of any sex.
The inventors during their search for new anti-obese supplements have screened
a large
number of plant extracts for anti-adipogenesis activity using an in vitro
assay in 3T3-L1
pre-adipocyte cells and found that extracts of Sphaeranthus indicus showed
potent anti-
adipogenic activity. Subsequent studies have shown that Sphaeranthus indicus
can
potently ameliorate a wide range of metabolic protein markers directly related
to obesity,
diabetes, cardiovascular diseases and other metabolic disorders. The anti-
obese efficacy
of Sphaeranthus indicus was confirmed in an in vivo study in diet induced
obesity and
diet induced metabolic syndrome models of Sprague Dawley rats. The details of
above
experiments and the study results are described in inventor's previous Indian
patent
application and the corresponding PCT application 224/CHE/2009 filed 2"1
February,
2009; PCT/IN2010/000053 filed 1st February, 2010.
In the present invention, a study was conducted using Sphaeranthus indicus
extract
standardized to 5% 7-hydroxyfrullanolide (LI12508) and a composition
(LI12507F)
containing Sphaeranthus indicus extract standardized to 5% 7-
hydroxyfrullanolide in
combination with Garcinia mangostana extract standardized to 10% cx-mangostin
(LI80018) to assess their efficacy as an anti-obese supplement in a double
blind placebo
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controlled study in obese human subjects. Sixty obese subjects (27.6 % male;
72.4 %
female; ages 22-50 years) were included in a randomized, double-blind, placebo-
controlled study of 56 days duration. The participants (BMI 30 to 40) were
randomized
into three groups; placebo, LI12508 group and LI12507F group. The participants
received
either 600 mg/day of LI12508 and 800 mg of LI12507F formulation in two divided
doses
or two identical placebo capsules and all of them remained on a calorie-
controlled diet
(2000 Calories/day) and 30 min walking for 8 weeks. Various parameters
including,
physical, anthropomorphic, biochemical and questionnaire based evaluation
including
quality of life. The S. indicus extract (LI12508) and its formulation LI12507F
provided
significant reduction in body weight in both the treatment groups and also
indicated
promise for their potential use in controlling serum triglyceride levels. In
addition, both
LI12508 and LI12507F also showed unexpectedly improved quality of life and
improved
energy, exercise ability and endurance in subjects supplemented with the
treatments when
compared the placebo treated group. This includes increased mobility,
increased walking
speed, increased walking distance, lack of fatigue, feeling untired, feeling
light and
active.
Encouraged by this surprising result, the inventors evaluated the ability of
the study
products LI12508 and LI12507F to enhance the ATP levels in a cellular model.
The
intracellular ATP level in the cells treated cells with LI12508 and LI12507F
were
measured by luminescence based ATP detection assay system, ATPlite
(PerkinElmer
Inc., Waltham, MA). Briefly, equal number of L6 Rat myocytes was plated in
each well
of a 96-well cell culture plate and cultured in DMEM supplemented with 10%
FBS. The
cells were treated with test samples (LI12508 and LI12507F) at 50 pg/mL.
Intracellular
ATP level was quantitatively estimated from a standard curve plotted with
luminescence
units vs. known concentrations of ATP and the results compared with that
obtained for
the control treated sample as summarized in the table 1. Both the Sphaeranthus
indicus
extract standardized to 5% 7-HF (LI12508) and its composition (LI12507F)
significantly
increased the ATP levels in the rat myocyte cells, when compared to the
control.
The Energy Endurance potential of LI12508 following oral administration was
further
evaluated in male and female Swiss albino mice. Swiss albino mice of 20 weeks
old were
selected and examined for health status and divided into three groups each
consisting of 6
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animals (3 males and 3 females). The control group animals were treatedp.o
with 0.5% of
CMC and treatment groups were treated once a day with the test compound
LI12508 at
100 mg/kg or 250 mg/kg body weight for one week. On day 7, one hour after the
treatment, the animals were tested for energy endurance with force swimming
test using
the SMART video tracking system (Panlab S.L.U). Resting time and its
percentage, slow
moving and its percentage, fast moving and its percentage, total path length
of swimming
and average velocity were analyzed using SMART video tracking software and the
data is
summarized in table 2.
Based on the results obtained, there was a dose dependent decrease in mean
resting time
in animals supplemented with 100 or 250 mg/kg of the test substance, LI12508.
This
mean reduction in resting time observed in treated groups is statistically
significant when
compared to control. In addition, the mean increase in slow swimming time,
fast
swimming time and average distance covered in both the treatment groups (100
mg/kg
and 250 mg/kg) supplemented with LI12508 is also significant, when compared to
control
group as shown figures 1 to 3. Significant increase in average velocity was
observed in
animals treated with 250 mg/kg p.o as compared to control group as depicted in
figure 4.
The increase in mean slow swimming time and mean fast swimming time reveals
that the
animals treated with LI12508 (100 mg/kg and 250 mg/kg) preferred to swim for a
longer
period of time instead of resting as observed in vehicle treated control
animals. The
increase in mean swimming velocity observed in 250 mg/kg LI12508 treated
animals,
further support the increase in mean distance covered by the animals in the
shorter period
of time as compared to other two groups. This indicates the animals treated
with LI12508
were very active and energetic during 15 minutes forced swimming period and
could tend
to swim either slow or fast most of the time rather than resting when compared
to control
group treated with 0.5% CMC. The longer distance covered at higher velocity
and shorter
resting times observed in LI12508 treated animals indicate that LI12508
improves energy
and endurance. Hence, it is obvious that supplementation of Sphaeranthus
indicus extract
can increase the energy levels and endurance potential.
The forgoing demonstrates that Sphaeranthus indicus extract standardized to 5%
7-
hydroxyfrullanolide (LI12508) and its composition in combination with Garcinia
mangostana extract standardized to 10% a-mangostin (LI12507F) could be potent
natural
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supplements to provide an onset, steady maintenance of energy, physical
endurance and
mental alertness in humans and animals.
Accordingly, in a major embodiment, the invention discloses a herbal
ingredient selected
from extracts and fractions standardized to at least one
frullanolide/eudesmanoid
sesquiterpene compound(s) derived from Sphaeranthus indicus or their
composition(s) for
onset and steady maintenance of energy and mental alertness. The sphaeranthus
derived
ingredients and its compositions are useful for enhancing physical activity,
physical
fitness, mental alertness, energy levels, stamina levels, circulatory health,
blood vessel
health or for better physical and mental health in a mammal.
In another embodiment the invention discloses the composition consisting of
Sphaeranthus indicus derived herbal ingredient in combination with at least
one
biologically active ingredient selected from extract of Garcinia mangostana
fruit rind,
Osmium basilicum, Zingiber officinalis, Tribulus terrestris, vitamins, amino
acids,
taurine, an extract of Ginkgo biloba, Rhodiola and an extract of guarana,
optionally in
combination with an excipient, diluent or carrier as a natural energy enhancer
to provide
an onset and steady maintenance of energy and mental alertness in a warm
blooded
animal or mammal in need thereof.
In another embodiment, the invention relates to at least one Sphaeranthus
indicus derived
herbal ingredient selected from the extracts and fractions standardized to 7-
hydroxyfrullanolide or its analogs or mixtures thereof as a natural energy
enhancer to
provide an enhanced physical or mental performance, onset and steady
maintenance of
energy and mental alertness in a mammal.
In yet another embodiment, the invention relates to a composition comprising
at least one
herbal ingredient selected from extract or fraction standardized to at least
one
frullanolide/eudesmanoid sesquiterpene compound(s) derived from Sphaeranthus
indicus
or their composition(s) in combination with at least one ingredient selected
from the
extracts, fractions or compounds derived from Garcinia mangostana, further
optionally
containing at least one ingredient selected from excipient, diluent, vitamins
or amino
acids, as a natural energy enhancer for enhancing physical or mental
performance, onset
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and steady maintenance of energy enhancing physical activity, physical
fitness, mental
alertness, energy levels, stamina levels, circulatory health, blood vessel
health or for
better mental health in a mammal.
In yet another embodiment, the invention provides a composition comprising at
least one
herbal ingredient selected from the extracts, fractions or compounds derived
from
Sphaeranthus indicus in combination with at least one ingredient selected from
the
extracts, fractions or compounds derived from Garcinia mangostana, optionally
containing at least ingredient selected from excipient, diluent, vitamins or
amino acids, as
a natural energy enhancer for enhancing physical or mental performance, onset
and
steady maintenance of energy and mental alertness in a mammal.
In another embodiment of the invention provides a composition comprising at
least one
herbal ingredient selected from the extracts or fractions standardized to at
least one
frullanolide/ eudesmanoid sesquiterpene compound such as 7-hydroxyfrullanolide
(1)
derived from Sphaeranthus indicus in combination with a Garcinia mangostana
extract
standardized to a-mangostin (2) or y-mangostin (3) and further optionally in
combination
with suitable excipients as a natural energy enhancer to provide an enhancing
physical or
mental performance, onset and steady maintenance of energy, mental alertness,
for
enhancing physical activity, physical fitness, energy levels, stamina levels,
circulatory
health, blood vessel health or for better mental health in a mammal.
Structures of 7-Hydroxyfrullanolide (1), a-mangostin (2) & y-mangostin (3)
0 OH
.00H RO
0 HO 0 OH
0 1 2. R = CH3
3. R = H
In still yet another embodiment of the invention provides a composition
comprising at
least one herbal ingredient selected from the extracts or fractions
standardized to 5% 7-
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hydroxyfrullanolide derived from Sphaeranthus indicus in combination with a
Garcinia
mangostana extract standardized to 10% a-mangostin and suitable excipients as
a natural
energy enhancer to provide an enhancing physical or mental performance, onset
and
steady maintenance of energy and mental alertness in a mammal.
In another important embodiment, examples of improved physical performance
include
increased stamina and improved speed, strength, power, endurance, flexibility,
agility,
balance, focus coordination, reaction time, fatigue recovery and also increase
of sex
stamina. Examples of improved mental performance include improved sharpness,
attention span, mental alertness, cognitive functions, mood elevation, and
recovery or
reduction of mental fatigue (e.g., following a high-intensity physical
exercise).
In another embodiment, the invention includes the preparation of dietary
supplements,
food ingredient formulations such as beverages, snacks and energy drinks
containing the
above said ingredient(s) or its composition(s) for enhancing physical
activity, physical
fitness, mental alertness, energy levels, stamina levels, circulatory health,
blood vessel
health or for better mental health in warm blooded animals in need thereof.
In yet another embodiment the invention provides at least one herbal
ingredient selected
from the extract(s), fraction(s), compound(s), extracts or fractions
standardized to active
compound(s)/7-hydroxyfrullanolide or its analogs derived from Sphaeranthus
indicus and
compositions as natural enhancers of energy instantly, physical performance in
warm
blooded animals in need thereof.
In another embodiment the extracts and/or fractions standardized to 7-
hydroxyfrullanolide, its analogs or their compositions can be used for
enhancing physical
performance or energy levels in warm blooded animals.
In yet another embodiment the invention provides compositions comprising
biologically
active ingredients in combination with one or more components selected from
extract(s),
fraction(s), active compound(s), phytochemical(s); powder(s) derived from
plant(s),
animal(s) or microorganisms with proven therapeutic health benefits;
pharmaceutically or
dietetically acceptable agents, active ingredients, vitamins, amino acids or
minerals.
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In the other embodiment, the invention discloses composition containing
Sphaeranthus
indicus extract or fraction standardized to 7-hydroxyfrullanolide or its
analogs in
combination with at least one biologically active ingredient selected from an
extract of
Garcinia mangostana, Osmium basilicum, Zingiber officinalis, Tribulus
terrestris, vitamin
B, vitamin C, Vitamin E, taurine, an extract of ginkgo biloba, Rhodiola and an
extract of
guarana.
In another embodiment of the invention discloses the composition consisting of
Sphaeranthus indicus derived herbal ingredient in combination with at least
one
biologically active ingredient selected from extract of Garcinia mangostana
fruit rind,
Osmium basilicum, Zingiber officinalis, Tribulus terrestris, vitamins, amino
acids,
taurine, an extract of Ginkgo biloba, Rhodiola and an extract of guarana,
optionally in
combination with an excipient, diluent or carrier as a natural energy enhancer
to provide
an onset and steady maintenance of energy and mental alertness in a warm
blooded
animal or mammal in need thereof.
In another embodiment the invention discloses the compositions wherein the
extract of
Garcinia mangostana fruit rind is standardized to a-mangostin or y-mangostin
or both and
optionally in combination with at least one excipient/diluent as a natural
energy enhancer
to provide an onset and steady maintenance of energy and mental alertness in a
warm
blooded animal or mammal in need thereof.
In a further exemplary embodiment, the biologically active ingredients of the
present
invention for preparing the composition may further include one or more of the
non-
limiting components such as vitamins selected from B vitamins, including
thiamine,
riboflavin, niacin, pantothenic acid, pyridoxine, biotin, cyanocobalamin,
choline and/or
folic acid, including the reduced forms of folic acid such as but not limited
to folinic acid,
calcium folinate and methyltetrahydrofolate. The B-complex vitamins are also
water
soluble vitamins that aid the breakdown of carbohydrates into glucose to
provide energy
for the body, the breakdown of fats and proteins to aid the normal functioning
of the
nervous system, and muscle tone in the stomach and intestinal tract.
Particular forms of B
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vitamins in the composition may include d-Calcium pantothenate, niacinamide,
pyridoxine hydrochloride, and thiamine mononitrate; or amino acids.
In another embodiment the Sphaeranthus indicus derived herbal ingredient
selected from
the extracts or fractions standardized to 7-hydroxyfrullanolide or its analogs
or mixtures
thereof and/or their composition(s) increases circulation, metabolism
efficiency, regulates
neurotransmitters and boosts oxygen levels in the brain. Benefits of enhanced
circulation
in the brain include improved short and long term memory, increased reaction
time and
improved mental clarity.
In yet another embodiment the said herbal ingredients or their composition(s)
are useful
for enhancing energy levels, mental alertness, stamina levels, circulatory
health and blood
vessel health as well as for providing nutritional support. It can also be
used as an energy
booster for patients in need thereof, e.g., cancer patients or AIDS patients.
Moreover, it is
useful for enhancing athletic performance in both humans and animals, e.g.,
horses.
In another embodiment the said herbal ingredients and/or their composition(s)
can be
taken e.g. by performance athletes, those engaged in endurance and multi-
discipline
sports, aged and sick persons in order to increase mental and physical
efficiency and to
repress susceptibility to illnesses, such as cold, bacterial and viral
infections, in a natural
manner. The present ingredients and compositions may be formulated as a
"fitness drink"
that can be taken with breakfast or in the form of a concentrate from which
such a drink
can be regularly used.
In another embodiment 7-hydroxyfrullanolide or its analogs obtained naturally,
synthesized or semi-synthesized can be useful for enhancing physical or mental
performance.
In another embodiment one or more of the analogs of 7-hydroxyfiullanolide that
can be
used for preparing compositions comprise of frullanolides; 11a,13-dihydro-
3a,7a-
dihydroxy-4,5 -epoxy-613,7-eudesmanol i de ; I1a,13-dihydro-7a-acetoxy-313-
hydroxy-613,7-
eudesm-4-enolide; 3-keto-13-eudesmol; I1a,13-dihydro-3a,7a-dihydroxyeudesm-4-
en-
6a,12-olide; 11a,13-dihydro-3a,7a-dihydroxyfrullanolide; 11 a,13-
dihydro-7a,13-
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dihydroxyfrul lanolide; 11a,13-dihydro-7a-hydroxy-13-methaoxyfrullanolide;
2a,7a-
dihydroxy-4-en-11,13 -dihydroeudesm-6,12-olide; 2a-hydroxycostic acid; 3-keto-
7a-
hydroxyeudesm-4-en-6,12-olide (cryptomeridiol); 4-
epicryptomeridiol;
sphaeranthanolide; 2a-hydroxysphaerantholide; 2a-acetoxysphaerantholide; 2a,7a-
dihydroxysphaerantholide; 2a-acetoxy-7a-hydroxysphaerantholide and 2a-acetoxy-
5a-
hydroxyisosphaerantholide.
The concentration of Sphaeranthus indicus derived 7-hydroxyfrullanolide or
frullanolide/
eudesmanoid sesquiterpene compounds in the present invention individually or
together
varies in the range of 0.01% to 99.99%.
The composition wherein, the concentration of Garcinia mangostana fruit rind
extract, a-
mangostin and 7-mangostin individually or jointly varies from 0.01% to 99.99%.
In another embodiment the herbal ingredient(s) or composition(s) of the
present invention
are useful to improve aerobic performance and capacity by influencing lactic
acid
metabolism and reducing fatigue as well as for alleviation of one or more of
the
biological energy markers including but not limited to ATP levels/production;
Nitric
Oxide levels, NADH balance, leptin levels, adipocytes derived peptide
In another embodiment the herbal ingredient(s) can further be combined with
one or more
biological active ingredients comprising anti-diabetic, anti-hyperlipidemic,
anti-obesity,
anti-hypertensive, anti-platelet aggregation, anti-infective, anti-
atherosclerotic, anti-
inflammatory, anti-oxidant and bio-enhancing activity.
In a further exemplary embodiment, the composition may contain an
effervescent. As is
understood, an effervescent is an agent comprising one or more compounds
which, act
individually or together, evolve a gas on contact with water. The gas evolved
is generally
oxygen or, most commonly, carbon dioxide. Preferred effervescent agents
comprise an
acid component and a base component that react in the presence of water to
generate
carbon dioxide gas. The acid component can comprise one or more acids and the
base
component can comprise one or more bases. Preferably, the base component
comprises an
alkali metal or alkaline earth metal carbonate or bicarbonate and the acid
component
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comprises an aliphatic carboxylic acid. Non-limiting examples of suitable
bases for use in
a base component include carbonate salts (e.g., calcium carbonate),
bicarbonate salts
(e.g., sodium bicarbonate), sesquicarbonate salts, and mixtures thereof.
Sodium
bicarbonate is a preferred base.
Non-limiting examples of suitable acids for use in an acid component include
citric acid,
lactic acid, glutaric acid, phosphoric acid, acetic acid, tartaric acid, malic
acid, fumaric
acid, adipic acid, succinic acid, oxaloacetate, acid anhydrides of such acids,
acid salts of
such acids, and mixtures thereof. Citric acid is a preferred acid.
In a further exemplary embodiment, the composition may contain sweeteners.
Preferred
sweeteners for use in the present invention are sugars and sugar alcohols such
as sucrose,
fructose, dextrose, maltose, lactose, high fructose corn syrup solids, invert
sugar, sugar
alcohols, including sorbitol, as well as mixtures of these sugars and sugar
alcohols. In
order to deliver lower levels of solids per dosage, it may be preferred to use
a higher
intensity sweetener with the sugar or sugar alcohol. These higher intensity
sweeteners
include saccharin, cyclamates, acesulfame K, L-aspartyl-L-phenylalanine lower
alkyl
ester sweeteners (e.g., aspartame); L-aspartyl-D-alanine amides; L-aspartyl-D-
serine
amides; L-aspartyl-L- 1 -hydroxymethylalkaneamide sweeteners;
L-aspartyl- 1 -
hydroxyethyalkaneamide sweeteners; and L-aspartyl-D-phenylglycine ester and
amide
sweeteners. Further sweeteners contemplated for use with the compositions
disclosed
herein include sweeteners derived from stevia, sweeteners derived from
momordica
grosvenorii, and sweeteners derived from mogrosides. A particularly preferred
sweetener
system is a combination of sucralose with acesulfame K and corn syrup solids.
In another exemplary embodiment, the composition may be dissolved in water or
in other
liquids suitable for human consumption.
In another embodiment of the invention the various suitable solvents that can
be used for
preparing the extracts and fractions or extracting or fractionating the herbs
such as
Sphaeranthus indicus, Garcinia mangostana include but not limited to Cl -05
alcohols,
like ethanol, methanol; water and mixtures thereof; C 1-C7 hydrocarbons such
as hexane;
esters like ethyl acetate and the like and mixtures thereof.
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In another embodiment, the ingredients and compositions of the present
invention may be
formulated in dry form, liquid form, food product, dietary supplement or any
suitable
form such as tablet, a capsule or a soft chew.
In another embodiment the herbal ingredient(s) or composition(s) can be
delivered in the
form of controlled release tablets, using controlled release polymer-based
coatings by the
techniques including nanotechnology, microencapsulation, colloidal carrier
systems and
other drug delivery systems.
In another embodiment of the invention provides herbal ingredient(s) or their
compositions nutritional/dietary supplements can be contemplated/made in the
dosage
form of healthy foods, or food for specified health uses such as solid food
like chocolate
or nutritional bars, semisolid food like cream or jam, or gel and also
beverage and the
like, such as refreshing beverage, lactic acid bacteria beverage, drop, candy,
chewing
gum, gummy candy, yoghurt, ice cream, pudding, soft adzuki bean jelly, jelly,
cookie,
tea, soft drink, juice, milk, coffee, cereal, snack bar and the like.
The flavorant(s) that may be included in the composition are not relevant to
the inventive
concepts disclosed herein, and those skilled in the art are familiar with the
wide range of
flavorants available. Therefore, any suitable flavorant or combination of
flavorants,
natural and/or artificial, is within the contemplated scope of the present
disclosure.
In another exemplary embodiment, the composition may further include food
colorants to
improve the visual appearance of a drink prepared with the composition.
The flavoring agent or agents may provide a fruit flavor, cola flavor, vanilla
flavor, or a
chocolate flavor, by way of example and not by way of limitation. Sweeteners,
natural or
synthetic, such as sucrose, sucralose, aspartame, and/or acesulfame potassium,
neotame,
polydextrose, glycerin, sorbitol, and xylitol, may be used, by way of example
and not by
way of limitation. Coloring agents may be added. Agents such as citric acid,
fumaric acid,
adipic acid, tartaric acid, and in some instances lactic acid may be added to
adjust for
tartness.
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Additional ingredients in the form of analgesics (e.g. aspirin), mild
stimulants other than
caffeine, which is mentioned above (e.g. green tea), or relaxants (e.g.
melatonin), may be
added in specialized product applications.
In other embodiment, the herbal ingredients and composition of this invention
are useful
in treating mitochondrial deficiencies in both humans and animals. It also can
be used for
enhancing or maintaining physical or mental performance, reducing infection in
physically stressed athletes or non-athletes from intense physical exercises.
Moreover, it
can be an activator of Sirtuin.
In another exemplary embodiment the biologically acceptable ingredients or
compositions can further be combined with one or more pharmaceutically or
dietetically
acceptable excipients, carriers and diluents, comprising glucose, fructose,
sucrose,
maltose, yellow dextrin, white dextrin, aerosil, microcrystalline cellulose,
calcium
stearate, magnesium stearate, sorbitol, stevioside, corn syrup, lactose,
citric acid, tartaric
acid, malic acid, succinic acid, lactic acid, L-ascorbic acid, dl-alpha-
tocopherol, glycerin,
propylene glycol, glycerin fatty ester, poly glycerin fatty ester, sucrose
fatty ester,
sorbitan fatty ester, propylene glycol fatty ester, acacia, carrageenan,
casein, gelatin,
pectin, agar, vitamin B group, nicotinamide, calcium pantothenate, amino
acids, calcium
salts, pigments, flavors, preservatives, distilled water, saline, aqueous
glucose solution,
alcohol, propylene glycol and polyethylene glycol, various animal and
vegetable oils,
white soft paraffin, paraffin and wax.
In still another embodiment, the invention features a method for enhancing
physical or
mental performance, steady maintenance of energy, physical endurance and
mental
alertness in humans and animals, wherein the method comprises administering to
a
subject in need thereof an effective amount of at least one herbal ingredient
selected from
the extract(s), fraction(s), compound(s), extracts or fractions standardized
to active
compound(s)/7-hydroxyfrullanolide derived from Sphaeranthus indicus and
compositions
thereof. Examples of improved physical performance include increased stamina
and
improved speed, strength, power, endurance, flexibility, agility, balance,
focus
coordination, reaction time, fatigue recovery and also increase of sex
stamina. Examples
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of improved mental performance include improved sharpness, attention span,
mental
alertness, cognitive functions, mood elevation, and recovery or reduction of
mental
fatigue (e.g., following a high-intensity physical exercise). By properly
administrating the
ingredient or composition, a subjects physical or mental performance can be
greatly
enhanced without deleterious side effects.
In still another embodiment, the invention features use of at least one herbal
ingredient
selected from the extract(s), fraction(s), compound(s), extracts or fractions
slandardized
to active compound(s)/7-hydroxyfrullanolide derived from Sphaeranthus indicus
and
compositions thereof to enhance physical activity, physical fitness, mental
alertness,
enhancing energy levels, stamina levels, circulatory health, blood vessel
health and for
better mental health in warm blooded animal or humans or animals.
In still another embodiment of the invention, use of at least one herbal
ingredient selected
from the extract(s), fraction(s), compound(s), extracts and fractions
standardized to active
compound(s)/7-hydroxyfrullanolide derived from Sphaeranthus indicus and
compositions
thereof for the preparation of a medicament useful for enhancing physical or
mental
performance, steady maintenance of energy, physical endurance and mental
alertness in
humans and animals.
Those of ordinary skill in the art will appreciate that changes could be made
to the
embodiments described above without departing from the broad inventive concept
thereof. It is understood, therefore, that this invention is not limited to
the particular
embodiments or examples disclosed, but is intended to cover modifications
within the
objectives and scope of the present invention as defined in the specification.
Example 1
Sphaeranthus indicus methanol extract (LI12500): Sphaeranthus indicus flower
heads (1
kg) were taken in a round bottom flask and extracted with methanol (8 L) at 60
- 65 C
temperature for 2 h. The extract was filtered and the spent raw material was
re-extracted
twice with methanol (2 x 6 L) under similar conditions. The combined extract
was fine
filtered and concentrated over a climbing film evaporator to obtain a residue
(110 g). The
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methanol extract (LI12500) showed 11% of 7-hydroxyfrullanolide by HPLC method
of
analysis.
Sphaeranthus indicus methanol extract standardized to 5% 7-hydroxyfrullanolide
Sphaeranthus indicus methanol extract containing 7-hydroxyfrullanolide as
obtained
above was diluted with microcrystalline cellulose and magnesium strearate
along with 2%
by weight of aerosil to obtain Sphaeranthus indicus powdered methanol extract
standardized to 5% 7-hydroxyfrullanolide (LI12508).
Example 2
Sphaeranthus indicus ethanol extract: Sphaeranthus indicus flower heads (1 kg)
were
taken in a RB flask and extracted with ethanol (8 L) at 60- 65 C temperature
for 2 h. The
extract was filtered and the spent raw material was re-extracted twice with
ethanol (2 x 6
L) under similar conditions. The combined extract was fine filtered and
concentrated over
a climbing film evaporator to obtain a residue (98 g). The ethanol extract
showed 12% of
7-hydroxyfrullanolide by HPLC method of analysis.
Example 3
Garcinia mangostana rind methanol extract (LI80013): Shade dried fruit rind
(1Kg) of
Garcinia mangostana was pulverized to coarse powder, and extracted with 90%
methanol
(5L) for 2 hrs at 60-65 C. The solvent was separated from the raw material by
filtration.
Extraction process was repeated three times using 90% methanol (2x3 L & 1x2
L). The
combined extracts were fine filtered and concentrated under reduced pressure
and
allowed to precipitate at ambient temperature. The solid separated was
filtered to give a
dry powder (150 g, a-mangostin: 21% and y-mangostin: 2.5%).
Example 4
Garcinia mangostana methanol extract standardized to 10% a-mangostin:
Garcinia mangostana methanol extract containing a-mangostin as obtained above
(example 3) was diluted with microcrystalline cellulose and magnesium
strearate along
with 2% aerosil to obtain Garcinia mangostana methanol extract standardized to
10% a-
mangostin (LI80018).
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Example 5
Garcinia mangostana rind ethanol extract: Shade dried fruit rind (1Kg) of
Garcinia
mangostana was pulverized to coarse powder, and extracted with 90% ethanol
(5L) for 2
hrs at 60-65 C. The solvent was separated from the raw material by filtration.
Extraction
process was repeated thrice using 90% ethanol (2x3 L & 1x2 L). The combined
extracts
were fine filtered and concentrated under reduced pressure and allowed to
precipitate at
ambient temperature. The solid separated was filtered to give ethanol extract
as a dry
powder (136 g, a-Mangostin: 22%).
Example 6
Composition LI12506F: The composition LI12506F was prepared by combining the
methanol extract of Sphaeranthus indicus (LI12500) and 90% methanol extract of
Garcinia mangostana (LI80013), both as prepared above, in the ratio of 3:1.
Example 7
Formulation LI12507F (Merastin ): The Sphaeranthus indicus powder extract
standardized to minimum 5% 7-hydroxyfrullanolide (LI12508) and Garcinia
mangostana
methanol extract standardized to 10% a-mangostin (LI80018) as prepared above
were
combined at 3: 1 ratio and properly blended to obtain LI12507F.
= Example 8
Composition LI12517F:
Composition LI12517F was prepared by mixing unit doses of the following
components:
One part of Sphaeranthus indicus ethanol extract (1 g) and
Three parts of Garcinia mangostana 90% ethanol extract (3 g).
Example 9
A study was conducted using Sphaeranthus indicus extract standardized to 5% 7-
hydroxyfrullanolide (LI12508) and a composition containing Sphaeranthus
indicus
extract standardized to 5% 7-hydroxyfnillanolide in combination with Garcinia
mangostana extract standardized to 10% a-mangostin (LI12507F) to assess their
efficacy
as an anti-obese supplement in a double blind placebo controlled study in
obese human
subjects. Sixty obese subjects (27.6 % male; 72.4 % female; ages 22-50 years)
were
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included in a randomized, double-blind, placebo-controlled study of 56 days
duration.
The participants (BM1 30 to 40) were randomized into three groups; placebo,
LI12508
group and L112507F group. The participants received either 600 mg/day of
LI12508 and
800 mg of LI12507F formulation in two divided doses or two identical placebo
capsules
and all of them remained on a calorie-controlled diet (2000 Calories/day) and
30 min
walking for 8 weeks. Various parameters including, physical, anthropomorphic,
biochemical and questionnaire based evaluation including quality of life have
been
studied. The S. indicus extract (LI12508) and its formulation L112507F
provided
significant reduction in body weight in both the treatment groups and also
indicated
promise for their potential use in controlling serum triglyceride levels.
Impact of Weight on Quality of Life Questionnaire-Lite Version (IWQ0L-Lite)
including
subjects feedback was administered to all the subjects at each evaluation
point including
days 0, 14, 28 and 56 was assessed. Subjects expressed improvement in various
parameters including increased mobility, increased walking speed, increased
walking
distance and time, feeling untired, feeling light and active. Number of
subjects expressed
such improvement in physical ability and endurance was more in supplement
groups
compared to placebo group.
Both LI12508 and LI12507F also showed unexpectedly improved quality of life
and
improved energy, exercise ability and endurance in subjects supplemented with
the
treatments when compared the placebo treated group. This includes increased
mobility,
increased walking speed, increased walking distance, lack of fatigue, feeling
untired,
feeling light and active.
Example 10
Intracellular ATP level in the cells treated cells with LI12508 and L112507F
were
measured by luminescence based ATP detection assay system, ATPlite
(PerkinElmer
Inc., Waltham, MA). Briefly, equal number of L6 Rat myocytes was plated in
each well
of a 96-well cell culture plate and cultured in DMEM supplemented with 10%
FBS. The
cells were treated with different concentrations of test samples (LI12508 and
LI12507F)
for 4h and thereafter, to each well 50 ul of cell lysis buffer were added. The
vehicle
, control culture wells received 0.2% DMSO (v/v). Finally, 50 ul of substrate
solution was
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added to each well and incubated at room temperature for 5 mm on plate shaker.
After 10
minutes of dark adaptation, the luminescence was read in a luminometer
(Modulus
Multimode Reader, Turner Biosystems Inc., Sunnyvale, CA). A serial dilution of
an ATP
standard solution ranging from 1x105 M to blank was applied to the assay
plate.
Intracellular ATP level was quantitatively estimated from a standard curve
plotted with
luminescence units vs. known concentrations of ATP.
Table 1
Dose ATP
S. No Test Product Code
pg/mL Concentration
1 Control 2.808
2 S. indicus 5% extract LI12508 50 3.313
3 S. indicus composition LI12507F 50
6.119
Example II:
Evaluation of Energy Endurance Capacity of herbal extract in Swiss albino
mice:
Eighteen Swiss albino mice of 20 weeks old were selected and examined for
health status
and acclimatized for one week before initiation of the study. The animals were
randomly
divided into three groups each consisting of 6 animals (3 males and 3 females)
corresponding to two doses (100 and 250mg/kg body weight) of test substance
LI12508
and vehicle control. The animals were treated orally with allocated test
substances or
vehicle daily for 1 week. Swimming exercise (15 min) was initiated after 1 hr
of
treatment and continued daily for 7 days. Mice were allowed to swim with
supporting
constant loads (lead fish sinkers, attached to the tail) corresponding to 10%
of their body
weight, in a acrylic tank filled with water. On day 7th, this swimming
exercise for 15 min
was tracked using the SMART video tracking system (Panlab S.L.U). Swimming
time or
resting time, Distance travelled and velocity of swimming was measured using
the
tracking software. Resting time and its percentage, moving slow and its
percentage,
moving fast and its percentage, total path length of swimming and average
velocity were
analyzed using SMART video tracking software and the data is summarized in
table 2.
There was a significant decrease in mean resting time and a significant
increase in mean
slow swimming time, mean fast swimming time and average distance covered in
both 100
mg/kg and 250 mg/kg of LI12508 treated group animals when compared to control
treated animal group as summarized in the figures 1 to 2. Moreover, animals
treated with
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250 mg/kg p.o showed a significant increase in average velocity as compared to
control
group as depicted in figure 4.
Table 2
Energy Endurance Potential of LI12508 on Forced Swimming Test Parameters
Paramete Restin Movin Movin Avera
Resting Movin Movin
rs Distance g g Slow g Fast ge
Time g Slow g Fast
Test (cm) Time Time Time Velocit
(Sec) (%) CYO
Article (%) (Sec) (Sec) y
39588.39 662.63 73.57 192.74 21.40 45.29 111.40
CMC 5.03
(Control) 1.44
5247.84 36.94 4.10 25.99 2.89 12.96 6.72
L112508 48345.11 64.83 27.87 116.27
574.63* 245.57* 7.30
100 ** 64.09*
0.71
mg/kg 2.90 2.33 5.36 2.71
31.56 19.48
2549.01
57160.52 125.96
L112508 565.71* 62.80 252.40*
28.02 82.71*
** 9.18 *
250 * * *
1.42
mg/kg 2.75 1.65
4810.60 6.39
24.78 14.82 12.83
Values are expressed as Mean S.E.M, n=6.
* p<0.05, **p<0.01 as compared to CMC control (ANOVA followed by Tukey's Test)
