WO2008006082A2

WO2008006082A2 - Energy enhancing formulation

Info

Publication number: WO2008006082A2
Application number: PCT/US2007/072982
Authority: WO
Inventors: Jon Barron
Original assignee: Jon Barron
Priority date: 2006-07-06
Filing date: 2007-07-06
Publication date: 2008-01-10
Also published as: WO2008006082A3

Abstract

An herbal formulation comprising mulungu, Bacopa monniera, green tea extract, L-theanine and, optionally, stevia is provided. The formulation, in preferred embodiments, energizes both the mind and body, stimulates the pleasure centers in the brain and body and acts as an appetite suppressant.

Description

ENERGY ENHANCING FORMULATION

Related Application

This application claims the benefit of United States Provisional Application No. 60/818,846, filed July 6, 2006, which application is hereby incorporated by reference in its entirety.

Field of the Invention

Preferred embodiments of the present invention relate to an energy enhancing formulation. More specifically, preferred embodiments relate to the use of a nutraceutical formulation comprising mulungu, Bacopa monniera, green tea, and L-theanine for increased energy, stimulation of pleasure centers in the mind and body, and/or appetite suppression.

Background of the Invention

Many energy formulations contain artificial ingredients, undesirable stimulants such as caffeine, and compounds, such as taurine, with unknown health effects. Although these formulations may provide an energy boost, they provide little or no additional health benefits.

Caffeine is a xanthine alkaloid compound that exhibits stimulatory properties in humans. Caffeine is a central nervous system stimulant and temporarily prevents drowsiness and restores energy and mental alertness. Accordingly, caffeine is a common ingredient in many energy drinks. However, many people are hypersensitive to the stimulatory properties of caffeine. Moreover, even individuals who can tolerate caffeine can experience adverse effects when exposed to the large amounts of caffeine often present in energy drinks.

High doses of caffeine can cause caffeine dependency, which can result in undesirable side effects such as anxiety, irritability, headaches, and heart palpitations. Caffeine may also be a factor in panic attacks and panic disorder.

The Applicant has previously described an energy enhancing formulation comprising mulungu, Bacopa monniera, and green tea. See http://www.jonbarron.org/barron_reports/2- l-2004.php (2004), herein incorporated by reference. However, embodiments of the present invention provide improved formulations comprising L-theanine. Summary of the Invention

In light of the above description regarding the adverse side effects of caffeine, there is a need for an energy drink that wards off drowsiness and increases alertness, without causing the adverse side effects or over-stimulation associated with caffeine or other stimulatory compounds. Preferred embodiments of the present invention provide an all-natural energizing formulation that provide an enhanced state of relaxed energy, and that also have other beneficial physiological effects. Preferred embodiments contain L-theanine to aid in inhibiting the stimulatory effects caffeine.

The Applicant has previously described an energy enhancing formulation comprising mulungu, Bacopa monniera, and green tea (http://www.jonbarron.org/barron_reports/2- 1 - 2004.php), herein incorporated by reference. However, the prior formulation did not contain L-theanine, which, as the Applicant discovered, offers several benefits, such as relaxation and the inhibition of caffeine's adverse effects.

The prior art discloses the use of theanine as a caffeine stimulation inhibitor. For example, U.S. Patent No. 5,501,866, herein incorporated by reference, discloses the use of theanine to counteract caffeine. However, U.S. Patent No. 5,501,866 discloses the use of theanine in quantities 10 to 500 times greater than the amount of caffeine. The use of such high concentrations of theanine has undesired side effects, as described further below.

Accordingly, preferred embodiments of the present invention comprise a formulation comprising mulungu, Bacopa monniera, green tea, and L-theanine in a concentration less than 10 times the amount of caffeine contained in the green tea. In one embodiment, similar inhibitory effects as those described in U.S. Patent No. 5,501,866 are achieved at lower dosages of L-theanine by combining L-theanine with mulungu, which acts as a sedative, to "smooth out" the consumption of a stimulant (e.g., caffeine in green tea). Thus, the combination of mulungu and L-theanine permit the use of lower doses of L-theanine to achieve the same effects as higher doses of theanine (as described in the prior art). The term "smooth out" or "smoothing out" as used herein, shall mean to negate the hyperactivity and/or hypertension associated with consumption of a stimulant, such as caffeine.

Thus, in one embodiment, the energy enhancing properties of caffeine are achieved with lower doses of caffeine and lower does of L-theanine than previously described because of the combined effects of mulungu. Thus, in one embodiment, unlike other energy formulations, additional or supplemental caffeine is not needed. In one embodiment, the only caffeine that is present is that which naturally occurs in the green tea.

In one embodiment, any one of the formulations described herein is used to reduce, inhibit or counteract the sedative effects of mulungu. In one embodiment, green tea is used to reduce, inhibit or counteract the sedative effects of mulungu. In one embodiment, L- theanine is used to reduce, inhibit or counteract the sedative effects of mulungu.

In one embodiment, the formulation comprises mulungu, wherein said mulungu is provided in a dosage of about 50 mg to about 600 mg, preferably about 150 mg to about 450 mg; Bacopa monniera, wherein said Bacopa monniera is provided in a dosage of about 50 mg to about 1000 mg, preferably 450 mg to about 900 mg; green tea, wherein said green tea is provided in a dosage of about 50 mg to about 900 mg, preferably 300 mg to about 600 mg; and L-theanine, wherein said L-theanine is provided in a dosage of about 5 mg to about 400 mg, preferably about 5 mg to about 200 mg. In one embodiment, the L-theanine is provided is independent from the L-theanine that is naturally occurring in the green tea. Thus, the green tea/bacopa/mulungu formulation is supplemented with additional L-theanine to provide advantageous and improved results.

In one embodiment, the formulations described herein are used to both stimulate and inhibit the central nervous system simultaneously. In one embodiment, the formulations described herein are used to both stimulate and relax the central nervous system via the action of gamma aminobutyric acid (GABA) or the neural or metabolic pathways in which GABA functions as a transmitter. In one embodiment, L-theanine, mulungu, and Bacopa activate the GABAnergic pathway, while the caffeine in the green tea inhibits the release of GABA. Thus, an optimal level of relaxation and mental alertness are achieved. This contrasts certain formulations of the prior art, which either stimulate or sedate.

In one embodiment, the amount of supplemental L-theanine that is added is less than 10 times the amount of caffeine present in the green tea. In one embodiment, the amount of caffeine present in the green tea is about 15 mg, and the amount of L-theanine that is added is in the range of about 15 mg to about 150 mg. In another embodiment, the amount of caffeine present in the green tea is in the range of about 5 mg to about 25 mg, and the amount of L- theanine that is added is in the range of about 50 mg to about 150 mg.

In any of the embodiments described herein, the concentration of green tea may contain less than about 50 mg of caffeine and the L-theanine may be provided in a dose of less than about 500 mg. Alternatively, less than about 30 mg of caffeine and about 30 mg to about 250 mg of L-theanine are provided. Alternatively, L-theanine is provided in a dose of less than 5, 6, 7, 8, 9, or 10 times the amount of caffeine present in the green tea. Alternatively, L-theanine is provided in a dose equal to or less than the amount of caffeine present in the green tea. In one embodiment, 25 mg of caffeine is provided, and 10, 15, or 20 mg of L-theanine is provided. In preferred embodiments, mulungu is provided and complements the use of L-theanine, and therefore less L-theanine is needed counteract the effects of the caffeine in the green tea.

In one embodiment, a sweetener is provided. In a preferred embodiment, the sweetener is stevia. In preferred embodiments, stevia is provided when the formulation is used as a supplement. In some embodiments, stevia is not used when the formulation is used as an ingredient (e.g., in a solid food or beverage). In several of the latter embodiments, the food or beverage is sufficiently sweet, and does not require the addition of a sweetener in the formulation. Likewise, in several of the latter embodiments, sweetness may not be desired.

In one preferred embodiment, an energy enhancing formulation is prepared in a glycerin base. The glycerin base, in some embodiments, provides increased stability and flavor.

In one embodiment, the formulation is provided as a nutritional supplement. In another embodiment, the formulation is provided as a food additive.

In a preferred embodiment, the formulation is provided in beverage form. In one embodiment, the formulation is added to a soft drink or an energy drink. In some embodiments, the formulation is provided as an ingredient in an energy bar or a nutritional bar.

In one embodiment, a method for enhancing energy in an individual is provided. In another embodiment, a method for stimulating pleasure centers in the brain and body is provided. In yet another embodiment, a method for suppressing the appetite is provided. In a further embodiment, a method for promoting both relaxation and mental alertness in an individual is provided.

In preferred embodiments, the methods disclosed herein comprise administering an effective dose of any one of the formulations described herein to an individual. Formulations may be administered as a preventative measure or as a curative.

In one embodiment, a formulation for down -regulating one or more stimulatory effects of caffeine or green tea is provided. In one embodiment, the formulation comprises mulungu, Bacopa monniera and L-theanine.

In one embodiment, a medicament, prepared using the formulations described above, for enhancing energy in an individual is provided. In another embodiment, a medicament, prepared using the formulations described above, for stimulating pleasure centers in the brain and body is provided, hi yet another embodiment, a medicament, prepared using the formulations described above, for suppressing the appetite is provided. In a further embodiment, a medicament, prepared using the formulations described above, for promoting both relaxation and mental alertness in an individual is provided.

In one embodiment, a formulation for down-regulating one or more stimulatory effects of green tea is provided. In one embodiment, the formulation comprises: mulungu in a dosage of about 150 mg to about 450 mg; Bacopa monniera in a dosage of about 450 mg to about 900 mg; and L-theanine in a dosage of about 1 to 5 times the amount of caffeine in the green tea.

In another embodiment, a formulation for down-regulating one or more stimulatory effects of caffeine is provided. In one embodiment, the formulation comprises: mulungu in a dosage of about 150 mg to about 450 mg; Bacopa monniera in a dosage of about 450 mg to about 900 mg; and L-theanine in a dosage of about 1 to 5 times the amount of caffeine.

Brief Description of the Drawings

Figure 1 shows the classification of brain waves and mental conditions. States increase from low (delta) to high (beta) energy states. Stimulants, such as caffeine, suppress theta and alpha waves, and promote beta waves, leading to increased stress, anxiety and depressed immune function. See WG Dimpfel, FG Schober, MG Spϋler. The influence of caffeine on human EEG under resting condition and during mental loads. Journal of Molecular Medicine, Mar. 93: 197 - 207, herein incorporated by reference.

Figure 2 shows the reduction in blood pressure in hypertensive rats treated with L- theanine. See Kakuda T, Nozawa A, Unno T, Okamura N, Okai O. Inhibiting effects of theanine on caffeine stimulation evaluated by EEG in the rat. Biosci Biotechnol Biochem. 2000 Feb. 64(2):287-93, herein incorporated by reference.

Detailed Description of the Preferred Embodiments

Preferred embodiments of the present invention relate to a formulation comprising mulungu, Bacopa monniera, green tea, and L-theanine. Stevia is optionally provided. Various parts of each plant (mulungu, Bacopa monniera, stevia) may be used, including, but not limited to, the root, stem, fruit or whole plant or tuber. Several embodiments include powders, extracts, components, or derivatives of mulungu, Bacopa monniera, green tea, L- theanine and/or stevia. The use of powders and/or extracts of the herbal components of the formulations provided herein is within the scope of preferred embodiments of the present invention.

In one embodiment, the ability of Bacopa to stimulate the pleasure centers of the brain is matched by the ability of mulungu to stimulate the pleasure centers of the body. Thus, in one embodiment, the formulation stimulates both neuronal receptors and non-neuronal receptors.

In one embodiment, the formulation comprises green tea. The green tea extract enhances energy levels, and its combination with mulungu prevents mulungu from working as a sedative (its usual application) and allows the formulation to act as a physical stimulant. Thus, in one embodiment, the invention comprises a method of counteracting the sedative effects of mulungu. hi a preferred embodiment, the formulation comprises Bacopa monniera, green tea, and L-theanine, and optionally comprises one or more sweeteners. Because a natural product is preferred in some embodiments, the formulation comprises stevia as a sweetener. hi several embodiments, the formulations described herein have the unique ability to energize both the mind and body, to stimulate the pleasure centers in the brain and body, and to act as an appetite suppressant. The additional physiological benefits provided by the formulations encompass the benefits of the individual components as discussed below. Mulungu

In several preferred embodiments, a formulation comprising mulungu is provided. Mulungu is a medium-sized, well-branched tree that produces many reddish-orange flowers at the ends of the tree's many branches. The tree is sometimes called "coral flower," as the flowers resemble the color of orange coral. Mulungu has typically been used as a sedative to calm agitation, nervous coughs and other nervous system problems including insomnia. Mulungu has also been used to quiet hysteria from trauma or shock, as a mild hypnotic sedative to calm the nervous system, to treat insomnia and to promote healthy sleeping patterns by sedating overactive neurotransmitters, to regulate heart palpations, for hepatitis, and for liver disorders.

The traditional use of mulungu for anxiety and stress was shown to alter anxiety- related responses. An animal model (correlating to human generalized anxiety disorder, as well as panic disorder) was undertaken on a water-alcohol extract of mulungu. See Ribeiro, M. D., "Effect of Erythrina velutina and Erythrina mulungu in rats submitted to animal models of anxiety and depression." Braz. J. Med. Biol. Res. 2006; 39(2): 263-70, herein incorporated by reference. This mulungu extract had an effect similar to the commonly prescribed anti-anxiety drug diazepam.

Normally, when taken by itself, mulungu can cause drowsiness. However, in preferred embodiments of the present invention, mulungu is used in combination with other ingredients to "smooth out" a stimulant. Thus, in some preferred embodiments, mulungu, L- theanine and green tea are used in combination to achieve an optimal stimulant effect. In one embodiment, using a combination of L-theanine, which does not act as a sedative, and mulungu requires the use of less mulungu to smooth out the caffeine in green tea. In one embodiment, using less mulungu would allow using less green tea to achieve the same level of stimulation. Too much green tea may cause problems due to exceedingly high levels of caffeine or polyphenols.

Further research has validated the traditional use of mulungu as an antimicrobial agent for throat and urinary infections. Mulungu has demonstrated antibacterial activity in two studies against Staphylococcus aureus, and antimycobacterial activity against Mycobacterium fortuitum and Mycobacterium smegmatis. See Tanaka, H., et al. Antibacterial activity of isoflavonoids isolated from Erythrina variegata against methicillin- resistant Staphylococcus aureus. Lett. Appl. Microbiol. 2002, 35(6):494-8; Telikepalli, H., et al. Isoflavonoids and a cinnamyl phenol from root extracts of Erythrina variegata. Phytochem. 1990, 29(6):2005-2007, all herein incorporated by reference. Thus, in one embodiment, a formulation comprising mulungu is provided as an antibacterial agent.

In one embodiment, about 150 mg to about 450 mg of mulungu are provided. In another embodiment, less than about 150 mg are provided, hi a further embodiment, more than about 450 mg are provided. In one embodiment, one of the following quantities of mulungu is added to a formulation comprising L-theanine, green tea, and Bacopa monniera: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 250 mg, 500 mg, 750 mg, 1000 mg and 2000 mg. In some embodiments, a dose comprising more than 2000 mg is provided. Bacopa monniera hi several preferred embodiments, a formulation comprising Bacopa is provided. Bacopa monniera is an Ayurvedic herb used in India for memory, epilepsy, and as a mild sedative. Bacopa commonly grows in marshy areas throughout India. Studies show that Bacopa has strong antioxidant properties and has been used effectively for hundreds of years as a rejuvenative for the brain and nervous system. It is believed to increase mental clarity, and to promote memory and intelligence. Bacopa also assists in heightening mental acuity and supports the physiological processes involved in relaxation. Bacopa is thought to help nourish neurons as it restores depleted synaptic activity. hi several preferred embodiments, formulations comprising Bacopa are provided, hi some embodiments of the invention, the formulations provide one or more of the following benefits:

• Improve memory

• Enhance episodic memory

• Increase learning speed and learning capacity

• Relieve stress and anxiety

• Support healthy cerebral function

• Promote awareness and perception

• Improve concentration and attention span • Diminish attention-deficit problems

• Balance emotional states

• Nourish and rejuvenates the mind

• Lower mental fatigue

• Protect the brain from free-radical damage

• Help in the handling of increasingly difficult tasks

• Promote vigilance

• Inhibit age-related cognitive decline

• increased novelty-seeking behavior, an attribute of intelligence associated with increased mental pleasure and increased lifespan.

In one embodiment, about 450 mg to about 900 mg of Bacopa monniera are provided. In another embodiment, less than about 450 mg are provided. In a further embodiment, more than about 900 mg are provided. In one embodiment, one of the following quantities of Bacopa monniera is added to a formulation comprising L-theanine, mulungu, and green tea: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 250 mg, 500 mg, 750 mg, 1000 mg and 2000 mg. In some embodiments, a dose comprising more than 2000 mg is provided. Green Tea

In several preferred embodiments, a formulation comprising green tea is provided. Green tea antioxidants are of the same family as grape seed and pine bark extracts. They are polyphenols, mainly flavonoids called proanthocyanidins. In green tea, the main proanthocyanidins are the catechins, and the most powerful of the catechins is Epigallocatechin Gallate (EGCG), found in the highest concentration in green tea. In some embodiments, the formulation comprises EGCG.

Green tea works to prevent tumors from developing the blood vessels they need to survive. Green tea has been shown to inhibit metastasis. Green tea is the first known natural telomerase inhibitor. Green tea is believed to eliminate the "immortality" of cancer cells. Green tea is particularly effective in destroying the causes of leukemia, prostate cancer, and breast cancer. Green tea has also been shown to be effective in regulating blood sugar, reducing triglycerides and in reversing the ravages of heart disease. Studies indicate that the Japanese, who drink large amounts of green tea, have some of the lowest rates of cardiovascular disease in the world. Green tea seems to be able to almost totally prevent cancer causing DNA damage in smokers — a possible explanation as to why the Japanese, who are among the world's heaviest smokers, have such a low incidence of lung cancer. In addition, green tea is an effective monoamine oxidase (MAO) inhibitor, protecting against brain-cell death from glucose oxidase, over-production of nitric oxide, and lowering the amount of free iron reaching the brain. Thus, green tea extract may play a major role in protecting against both Parkinson's and Alzheimer's disease. hi one embodiment, about 300 mg to about 900 mg of green tea are provided. In one embodiment, about 450 mg to about 600 mg of green tea are provided. In yet another embodiment, less than about 450 mg are used. In a further embodiment, more than about 900 mg are provided. In one embodiment, one of the following quantities of green tea is added to a formulation comprising L-theanine, mulungu, and Bacopa monniera: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 250 mg, 500 mg, 750 mg, 1000 mg and 2000 mg. In some embodiments, a dose comprising more than 2000 mg is provided.

The caffeine contained in the green tea is present in the following amounts, according to some embodiments: 0 mg, 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 60 mg, 70 mg, 80 mg, 90 mg, and 100 mg. More than 100 mg is provided in some embodiments.

Because green tea alone may have some undesirable effects, in some preferred embodiments, a formulation comprising green tea, L-theanine, mulungu, and preferably Bacopa are used in combination to achieve an optimal stimulant effect. L-Theanine hi several preferred embodiments, a formulation comprising L-theanine (gamma- ethylamino-L-glutamic acid) is provided. The L-theanine is added to a formulation comprising green tea in order to supplement the small amount of L-theanine found in green tea. By adding L-theanine separately, the beneficial effects from using L-theanine are increased while keeping the amount of green tea constant, which avoids undesirable effects such as exceedingly high caffeine or polyphenol levels. If L-theanine levels were raised merely by increasing the amount of green tea in the formulation, the higher levels of caffeine might cause harmful effects such as insomnia, headaches, nervousness, irritability, anxiety, and heart palpitations. See Leson, C. L., et al. Caffeine overdose in an adolescent male. J Toxicol Clin Toxicol; 1988;26(5-6):407-l 5, herein incorporated by reference. Furthermore, because caffeine increases the production of stomach acid, high usage over time can lead to ulcers and gastroesophageal reflux disease. In addition, exceedingly high levels of polyphenols can possibly cause liver and kidney damage. In laboratory studies, administering high concentrations of polyphenols, including the EGCG found in green tea, on animals resulted in dose-dependent toxicity and death. Data from these studies suggests that exceedingly high doses of EGCG can induce toxicity in the liver, kidneys, and intestine. Vomiting and diarrhea were also observed. See Lambert J.D., Sang S., and Yung C. S.; Possible Controversy over Dietary Polyphenols: Benefits vs. Risks. Chemical Research in Toxicology 2007; 20:583-585, herein incorporated by reference. Thus, preferred embodiments comprise both green tea and L-theanine added separately in levels higher than found naturally in green tea.

L-theanine is a free (non-protein) amino acid found almost exclusively in tea plants {Camellia sp.), constituting between 1 and 2-percent of the dry weight of tea leaves. It is the predominant amino acid in green tea leaves, giving tea its characteristic umami or "5th taste" (besides the four traditional tastes: sweet, salty, acid, and bitter). Attempts to isolate L- theanine, with its physical and neurological benefits, from tea leaves were once difficult, expensive, and inefficient. Economically feasible methods of producing the identical L- theanine now exist and do not require a mountain of tea leaves. Accordingly, using L- theanine or L-theanine and green tea have several advantages over using green tea alone.

In addition to the economic advantages of supplementing a green tea formulation with L-theanine, the supplementation also provides benefits such as promoting increased relaxation and mental alertness.

The calming effect of green tea may seem contradictory to the stimulatory property of tea's caffeine content but it can be explained by the action of L-theanine. This amino acid actually acts antagonistically against the stimulatory effects of caffeine on the nervous system. Research on human volunteers has demonstrated that L-theanine creates a sense of relaxation in approximately 30-40 minutes after ingestion via at least two different mechanisms. First, this amino acid directly stimulates the production of alpha brain waves, creating a state of deep relaxation and mental alertness similar to what is achieved through meditation. Second, L-theanine is involved in the formation of the inhibitory neurotransmitter, gamma amino butyric acid (GABA). GABA influences the levels of two other neurotransmitters, dopamine and serotonin, producing the key relaxation effect.

The brain emits weak electrical impulses (brain waves) that can be measured on the surface of the head. The predominant frequency of electrical impulses correlates with different types of mental states and activities. Brain waves are classified into four categories (delta, theta, alpha, and beta) — each with an associated mental state (Fig. 1). Delta is seen only in the deepest stages of sleep. Theta is seen in light sleep and drowsiness. Alpha is present in wakefulness where there is a relaxed and effortless alertness and Beta is seen in highly stressful situations and where there is difficulty in mental concentration and focus. Alpha brain waves are generated during a relaxed state and therefore alpha waves are used as an index of relaxation.

In one study of these mental responses to L-theanine, brain wave topography showed that alpha waves were observed from the back to the top of a person's head (occipital and parietal regions of the brain) within approximately 40 minutes after the subjects had taken either 50 or 200 mg of L-theanine. See Mason R. 200 mg of Zen; L-theanine boosts alpha waves, promotes alert relaxation. Alternative & Complementary Therapies 2001, April; 7:91- 95, herein incorporated by reference. In a separate study, the intensity of alpha waves were determined to be dose dependent (with a 200 mg dose showing a significant increase over controls) and detectable after 30 minutes. See Juneja LR, Chu D-C, Okubo T, et al. L- theanine a unique amino acid of green tea and its relaxation effect in humans. Trends Food Sci Tech 1999; 10:199-204, herein incorporated by reference. Thus, in one embodiment, a formulation comprising L-theanine is provided to increase the frequency or number of alpha brain waves. Certain embodiments of the present invention will allow the use of lower concentrations of L-theanine to achieve comparable effects.

L-theanine has a significant effect on the release or reduction of neurotransmitters like dopamine and serotonin, resulting in improved memory and learning ability. L-theanine may also influence emotions due to its effects on the increased release of dopamine. L-theanine reduces brain serotonin concentration by either curtailing serotonin synthesis or increasing degradation in the brain. The regulation of blood pressure is partly dependent upon catecholaminergic and serotonergic neurons in both the brain and the peripheral nervous system. Studies on spontaneously hypertensive rats (SHR) showed an impressive blood pressure lowering effect with L-theanine. The lowered blood pressure effect was dose-dependent with the highest test dose creating the most significant drop. L-glutamine was used as one of the controls. Although L-glutamine is similar in chemical structure to L-theanine, it did not exhibit an anti-hypertensive effect (Fig. 2).

Preliminary studies report that L-theanine has been found to increase the anti-tumor activity of some chemotherapeutic agents (doxorubicin and idarubicin) and to ameliorate some of the side effects of these drugs. It appears to increase the inhibitory concentration of these drugs in the tumor cells, although the mechanism is not known. At the same time, L- theanine decreased oxidative stress caused by these agents on the normal cells, possibly due to its mild antioxidant activity. In this regard, L-theanine has been shown to inhibit lipid peroxidation, catalyzed by copper, in low-density lipoprotein (LDL) in vitro.

Stress and anxiety are debilitating conditions that upset the balance of our hormones leading to a loss of our well-being, performance, and even lifespan. Stress impairs the immune system, leaving us vulnerable to opportunistic infections, and can cause depression. In 1998, sales of anti-anxiety drugs totaled over 700 million dollars, while sales of antidepressants totaled close to 5 billion dollars. Thus, in several preferred embodiments a formulation comprising L-theanine is provided. In one embodiment, the formulation is marked to and used by individuals to relieve stress. People under stress can mitigate many of the harmful effects of stress with L-theanine without becoming sedated in the process. In one embodiment, L-theanine will not make the user drowsy or promote sleep because it will not produce theta waves in the brain. In some embodiments, L-theanine would not produce further relaxation if an individual were already relaxed.

L-theanine has just recently been introduced to the U.S. market. Japan is credited with most of the clinical studies and information we possess thus far on L-theanine, but research is ongoing. L-theanine is absorbed from the small intestine via a sodium-coupled active transport process. L-theanine appears to cross the blood-brain barrier, as evidenced by the mental effects. L-theanine competes for absorption in the intestinal tract and the brain with the amino acids found in the methionine group (leucine, isoleucine, and valine), however the concentrations of amino acids are unchanged by simultaneous ingestion of L- theanine.

Researchers are studying L-theanine as an alternative to Ritalin in children and adults, as a treatment for PMS, in controlling certain conditions of high blood pressure, in sharpening mental acuity and concentration, and as an anti-cancer agent alone and in synergy with other cancer-fighting agents.

The intended use of L-theanine is that of a mental and physical relaxant that does not induce drowsiness. Thus, in some embodiments, a formulation comprising L-theanine is taken at the first signs of stress. In one embodiment, L-theanine is used in the range of 50- 200 mg, with the effect being felt within 30 minutes and lasting for 8-10 hours. Individuals with high stress levels may increase their dosage of L-theanine to at least 100 mg.

There are no known adverse reactions to L-theanine and no drug interactions have been reported. L-theanine is not affected by food and may be taken anytime, as needed. Because it has a mild taste, capsules may be opened and dissolved in water.

In one embodiment, about 50 mg to about 200 mg of L-theanine are provided, hi another embodiment, less than about 50 mg are provided, hi a further embodiment, more than about 200 mg are provided. In one embodiment, one of the following quantities of L- theanine is added to a formulation comprising green tea, mulungu, and Bacopa monniera: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 250 mg, 500 mg, 750 mg, 1000 mg and 2000 mg. In some embodiments, a dose comprising more than 2000 mg is provided.

In one embodiment of the present invention, L-theanine is used as a supplement in reducing the negative side effects of caffeine brought on by the over-consumption of coffee, soft drinks, or other caffeine-containing substances. Preferably, L-theanine is used in a formulation comprising mulungu, Bacopa, and in some embodiments, stevia. In one embodiment, the formulation comprises L-theanine in concentrations of about 1 to 5 times the amount of caffeine present, hi other embodiments, the formulation comprises L-theanine in concentrations of about 1 to about 5 times the amount of caffeine present. In other embodiments, L-theanine in provided at a concentration less than 10 times the amount of caffeine present. In one embodiment, the amount of L-theanine added is less than 10 times the amount of caffeine present in the green tea. In one embodiment, the amount of caffeine present in the green tea is about 15 mg, and the amount of L-theanine is 15 mg, 25 mg, 50 mg, 75 mg, 100 mg, 125 mg, or 150 mg. In another embodiment, the amount of caffeine present in the green tea is in the range of about 5 mg to about 50 mg, and the amount of L-theanine that is added is in the range of about 5 mg to 50 mg, and 50 mg to 500 mg. For example, in one embodiment, the amount of caffeine is 50 mg, and the amount of L-theanine is between about 50 mg to about 200 mg. In one preferred embodiment, the amount of L-theanine does not need to be higher than 10 times the amount of caffeine in the green tea, as recited in U.S. Patent No. 5,501,866, because of the synergistic or complementary effects of mulungu. Moreover, the caffeine concentration need not be excessive because of the synergistic or complementary effects of Bacopa monera.

In one embodiment, L-theanine derived from tea leaves is provided. In another embodiment, raw L-theanine is provided. In one embodiment, crude L-theanine is provided. In yet another embodiment, synthetic L-theanine is provided. Stevia

In preferred embodiments, stevia is provided when the formulation is used as a supplement. In some embodiments, stevia is not used, or is optional, when the formulation is used as an ingredient. Stevia is a South American shrub whose leaves have been used for centuries by native peoples in Paraguay and Brazil to sweeten beverages. Stevioside, the main ingredient in stevia (the two terms are often used interchangeably), is virtually calorie- free and hundreds of times sweeter than table sugar, so it appeals to many people as a natural alternative to artificial sweeteners. To the extent that stevioside is a different compound as stevia, stevioside can be used instead of or in addition to stevia in any of the embodiments described herein.

Whether in dry-leaf or concentrate form, stevia helps the body to correct both high and low blood sugar. Stevia also appears to lower blood pressure, but does not seem to affect normal blood pressure. In addition, stevia inhibits the growth and reproduction of harmful bacteria and other infectious organisms, including the bacteria that cause gum disease and tooth decay, and in many countries is used in oral-hygiene products. This ability of stevia to destroy infectious organisms may help explain why stevia users report a lower incidence of colds and flu.

In some embodiments, stevia is used as a supplement, together with the various formulations described herein, and is not used as a sweetening agent.

Although a formulation comprising stevia is preferred in several embodiments, other sweetening agents may also be used for some applications, including, but not limited to, honey, sucralose, organic brown sugar, and other forms of sucrose and sugar substitutes, including monosaccharides and disaccharides. In some embodiments, where sweetness is not desired, a sweetening agent such as stevia is not provided in the formulation.

In one embodiment, about 50 mg to about 500 mg of stevia are provided. In another embodiment, less than about 50 mg are provided. In a further embodiment, more than about 500 mg are provided. In one embodiment, one of the following quantities of stevia is added to a formulation comprising green tea, L-theanine, mulungu, and Bacopa monniera: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 250 mg, 500 mg, 750 mg, 1000 mg and 2000 mg. In some embodiments, a dose comprising more than 2000 mg is provided. Formulations

In one embodiment, the present invention provides a composition or formulation comprising mulungu, Bacopa monniera, green tea extract, and L-theanine. In one embodiment, the formulation additionally comprises stevia. The terms composition and formulation, as used herein, may be used interchangeably. In several preferred embodiments, the formulation is provided in a glycerin base for stability and an improved flavor profile. Providing the formulation in a glycerin base has several advantages. For example, using glycerin adds stability to the formulation and facilitates its use in beverages. A glycerin base also provides improved flavor

The formulation may also be provided in other suitable mediums, such as in an alcohol base (e.g., about 45-55% ethanol) for certain applications. In one embodiment, the invention provides a formulation in an alcohol base (e.g., about 45-55% ethanol), comprising mulungu, Bacopa monniera, green tea and optionally stevia, but lacking L-theanine.

In one embodiment, a formulation comprising mulungu, Bacopa monniera, green tea extract, and L-theanine is made by combining equal parts (by weight) of each of mulungu, Bacopa monniera, green tea extract, L-theanine and, optionally, stevia (all available commercially). Grinding, or other mechanical means, is used to achieve small consistent particles. A solvent of 50% dH₂O and 50% alcohol is used as a solvent to dissolve the ingredients. In a preferred embodiment, the alcohol is evaporated and glycerin is added for stability and flavor.

In one embodiment, mulungu, green tea and Bacopa are provided in a raw unprocessed form and combined to form a batch. The batch is ground to an ultra fine powder and put in large stainless steel vats. A solvent solution of water and alcohol is added to the top of the vat. The batch is brewed for 1-3 weeks, and mixed periodically. At the end of the brew cycle, the brew is run through a hydraulic press strainer, which squeezes out all of the liquid. Theanine is then added to the liquid. Approximately 3 g of liquid are used per serving. Less than 3 g or more than 3 g can also be used. Approximately half of the serving size is alcohol or (or another inactive solvent). Thus, in each serving, there are about 1.5 g of bioactive compounds, hi other embodiments, more or less than 1.5 g of bioactives are used. hi one embodiment, a formulation comprising 1-25% (wt %) of mulungu, Bacopa monniera, green tea and L-theanine is provided

In some embodiments, formulations comprising mulungu, Bacopa monniera, green tea and L-theanine additionally comprise one or more of the following agents or compounds: stevia, vitamins, minerals, antioxidants, and enzymes. In one embodiment, the formulation comprises mulungu, Bacopa monniera, green tea, L-theanine, stevia, and one or more of the following: Vitamin A, Vitamin B, Vitamin E, Vitamin C, Vitamin E, Vitamin D, Vitamin K, Zinc, Essential Fatty Acids, Ginko, Ginseng and Omega-3 Fatty Acids. hi one embodiment, the formulations described herein are prepared for use as a supplement. The formulations may be provided as tinctures, capsules and tablets for oral use. In another preferred embodiment, formulations may be provided as an additive to foods. Food products to which the compositions described above may be added include, but are not limited to beverages, baked goods, soups, cereals and packaged foods. Energy bars or nutritional bars may be particularly suitable for the addition of the formulations described herein. Suitable beverages include soft drinks such as coffee, tea, herbal tea, milk, fruit juice, water, carbonated beverages (e.g., soda, water, juice), soy milk and rice milk. The compositions may also be added to alcoholic beverages (e.g., beer, wine, hard liquor).

In some embodiments, concentrations in the range of about 0.01% to about 50%, preferably about 1% to about 20%, and more preferably about 5% to about 15% of the formulations described herein are added to food products. In other embodiments, concentrations less than 0.01% and greater than 50% are added to food products. In one embodiment, 1 ml of formulation is added for every 100 ml of beverage (e.g., soft drink or energy drink). In another embodiment, the formulation is provided in powder form, and added to the beverage during the manufacturing process.

In one preferred embodiment, a powdered form is not used. Instead, a glycerin based syrup form is provided. In one embodiment, about 3 ml to about 4.5 ml per serving is provided, hi one embodiment, the formulation will comprise .5 - 10% of the total volume of the beverage to which it is added.

In a preferred embodiment, a formulation comprising mulungu, Bacopa monniera, green tea, and L-theanine is provided in a beverage form to provide an energy drink, hi another embodiment, a formulation comprising mulungu, Bacopa monniera, green tea, and L- theanine is added to soft drinks, either during the manufacturing process or after the user has purchased and opened the drink, hi the latter embodiment, the formulation is provided in a tincture for addition by the consumer.

Another embodiment of the present invention comprises a method for enhancing energy by administering the formulations described above to an individual. In one aspect of this embodiment, an individual in need of enhanced energy is identified prior to administering the formulation. The formulation may be self-administered, or administered by another individual.

A further embodiment of the present invention comprises a method for stimulating the pleasure centers of the brain and body by administering the formulations described above to an individual, hi one aspect of this embodiment, an individual in need of stimulation of the pleasure centers is identified prior to administering the formulation. The formulation may be self-administered, or administered by another individual. Yet another embodiment of the present invention comprises a method for suppressing the appetite by administering the formulations described above to an individual. In one aspect of this embodiment, an individual in need of suppressed appetite (e.g., an overweight or obese individual) is identified prior to administering the formulation. The formulation may be self-administered, or administered by another individual.

The compositions described herein can be used per se, or in compositions where they are mixed with other active ingredients, suitable carriers or excipient(s). Techniques for formulation and administration of the compounds of the instant application may be found in "Remington's Pharmaceutical Sciences," Mack Publishing Co., Easton, PA, 18th edition, 1990.

The formulations according to several embodiments described herein may be administered via several routes of administration. Suitable routes of administration include, but are not limited to, oral, buccal, sublingual, rectal, topical, transmucosal, or intestinal administration; parenteral delivery, including intramuscular, subcutaneous, intravenous, intramedullary injections, as well as intrathecal, direct intraventricular, intraperitoneal, intranasal, or intraocular injections.

Alternatively, one may administer the compound in a local rather than systemic manner, for example, via injection of the compound directly in the renal or cardiac area, often in a depot or sustained release formulation. Further, one may administer the composition in a targeted delivery system, for example, in a liposome coated with a tissue-specific antibody. The liposomes will be targeted to and taken up selectively by the organ. Controlled release oral formulations are also provided in one embodiment.

The compositions of the several embodiments of the present invention may be manufactured in a manner that is itself known, e.g., by means of conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping or tabletting processes.

Compositions for use in accordance with preferred embodiments of the present invention thus may be formulated in conventional manner using one or more physiologically acceptable carriers comprising excipients and auxiliaries which facilitate processing of the active compounds into suitable preparations. Proper formulation is dependent upon the route of administration chosen. Any of the well-known techniques, carriers, and excipients may be used as suitable and as understood in the art; e.g., in Remington's Pharmaceutical Sciences, above.

For injection, the agents of the invention may be formulated in aqueous solutions, preferably in physiologically compatible buffers such as Hanks' s solution, Ringer's solution, or physiological saline buffer. For transmucosal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art.

For oral administration, the compounds can be formulated readily by combining the active compounds with carriers well known in the art. Such carriers enable the compounds of the invention to be formulated as tablets, pills, dragees, capsules, liquids, gels, syrups, slurries, suspensions, tinctures and the like, for buccal administration, sublingual administration or oral ingestion. Preparations for oral use can be obtained by mixing with one or more solid excipients, optionally grinding the resulting mixture, and processing the mixture of granules, after adding suitable auxiliaries, if desired, to obtain tablets or dragee cores. Suitable excipients are, in particular, fillers such as sugars, including lactose, sucrose, mannitol, or sorbitol; cellulose preparations such as, for example, maize starch, wheat starch, rice starch, potato starch, gelatin, gum tragacanth, methyl cellulose, hydroxypropylmethyl-cellulose, sodium carboxymethylcellulose, and/or polyvinylpyrrolidone (PVP). If desired, disintegrating agents may be added, such as the cross-linked polyvinyl pyrrolidone, agar, or alginic acid or a salt thereof such as sodium alginate.

For topical administration, the compounds may be formulated for administration to the epidermis as ointments, gels, creams, pastes, salves, gels, creams or lotions, or as a transdermal patch. Ointments and creams may, for example, be foπnulated with an aqueous or oily base with the addition of suitable thickening and/or gelling agents. Lotions may be formulated with an aqueous or oily base and will in general also containing one or more emulsifying agents, stabilizing agents, dispersing agents, suspending agents, thickening agents, or coloring agents.

Dragee cores are provided with suitable coatings. For this purpose, concentrated sugar solutions may be used, which may optionally contain gum arabic, talc, polyvinyl pyrrolidone, carbopol gel, polyethylene glycol, and/or titanium dioxide, lacquer solutions, and suitable organic solvents or solvent mixtures. Dyestuffs or pigments may be added to the tablets or dragee coatings for identification or to characterize different combinations of active compound doses.

Preparations which can be used orally, including sublingually, which include push-fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. The push-fit capsules can contain the active ingredients in admixture with filler such as lactose, binders such as starches, and/or lubricants such as talc or magnesium stearate and, optionally, stabilizers. Pn soft capsules, the active compounds may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols. In addition, stabilizers may be added. Formulations for oral administration should be in dosages suitable for such administration.

For buccal administration, the compositions may take the form of tablets lozenges or tinctures formulated in conventional manner.

For administration by inhalation, the compounds for use according to several embodiments of the present invention are conveniently delivered in the form of an aerosol spray presentation from pressurized packs or a nebulizer, with the use of a suitable propellant, e.g., dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide, or other suitable gas. In the case of a pressurized aerosol the dosage unit may be determined by providing a valve to deliver a metered amount. Capsules and cartridges of, e.g., gelatin for use in an inhaler or insufflator may be formulated containing a powder mix of the compound and a suitable powder base such as lactose or starch.

The compounds may be formulated for parenteral administration by injection, e.g., by bolus injection or continuous infusion. Formulations for injection may be presented in unit dosage form, e.g., in ampoules or in multi-dose containers, with an added preservative. The compositions may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents.

Formulations for parenteral administration include aqueous solutions of the active compounds in water-soluble form. Additionally, suspensions of the active compounds may be prepared as appropriate oily injection suspensions. Suitable lipophilic solvents or vehicles include fatty oils such as sesame oil, or synthetic fatty acid esters, such as ethyl oleate or triglycerides, or liposomes. Aqueous injection suspensions may contain substances which increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. Optionally, the suspension may also contain suitable stabilizers or agents which increase the solubility of the compounds to allow for the preparation of highly concentrated solutions.

Alternatively, the active ingredient may be in powder form for constitution with a suitable vehicle, e.g., sterile pyrogen-free water, before use.

The compounds may also be formulated in rectal compositions such as suppositories or retention enemas, e.g., containing conventional suppository bases such as cocoa butter or other glycerides.

In addition to the formulations described previously, the compounds may also be formulated as a depot preparation. Such long acting formulations may be administered by implantation (for example subcutaneously or intramuscularly) or by intramuscular injection. Thus, for example, the compounds may be formulated with suitable polymeric or hydrophobic materials (for example as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt.

Compositions suitable for use according to several embodiments of the present invention include compositions where the active ingredients are contained in an amount effective to achieve its intended purpose. More specifically, an effective amount means an amount of compound effective to enhance energy levels, stimulate pleasure centers in the brain and/or body, or to suppress the appetite. Determination of an effective amount is well within the capability of those skilled in the art, especially in light of the detailed disclosure provided herein.

It will be understood by those of skill in the art that numerous and various modifications can be made without departing from the spirit of the present invention. Therefore, it should be clearly understood that the forms of the present invention are illustrative only and are not intended to limit the scope of the present invention.

Claims

WHAT IS CLAIMED IS:

1. An energy enhancing formulation comprising: mulungu, wherein said mulungu is provided in a dosage of about 150 mg to about 450 mg;

Bacopa monniera, wherein said Bacopa monniera is provided in a dosage of about 450 mg to about 900 mg; green tea, wherein said green tea is provided in a dosage of about 300 mg to about 600 mg; and

L-theanine, wherein said L-theanine is provided in a dosage of about 5 mg to about 200 mg.

2. The formulation of Claim 1, wherein said L-theanine is independent of the green tea.

3. The formulation according to any one of the preceding claims, wherein said green tea comprises about 25 mg of caffeine and wherein said L-theanine is provided in a dose of about 25 mg to about 200 mg.

4. The formulation according to Claim 3, wherein said green tea comprises less than about 20 mg of caffeine and wherein said L-theanine is provided in a dose of about 20 mg to about 150 mg.

5. The formulation according to any one of the preceding claims, wherein said L- theanine is provided in a dose of less than 10 times the amount of caffeine present in said green tea.

6. The formulation according to Claim 5, wherein said L-theanine is provided in a dose of less than 5 times the amount of caffeine present in said green tea.

7. The formulation according to any one of the preceding claims, wherein any sedative effects of mulungu are inhibited by the interaction with said green tea.

8. The formulation according to any one of the preceding claims, further comprising a sweetener.

9. The formulation of Claim 8, wherein said sweetener is stevia.

10. The formulation according to any one of the preceding claims, further comprising a glycerin base.

11. The formulation according to any one of the preceding claims, wherein said formulation is provided as a nutritional supplement.

12. The formulation according to any one of the preceding claims, wherein said L- theanine is extracted from tea leaves.

13. The formulation according to any one of the preceding claims, wherein said L- theanine is crude L-theanine or raw L-theanine.

14. The formulation according to any one of the preceding claims, wherein said formulation is provided as a food additive.

15. The formulation according to any one of the preceding claims, wherein said formulation is provided in beverage form.

16. The formulation according to any one of the preceding claims, wherein said formulation is added to a soft drink or an energy drink.

17. The formulation according to any one of the preceding claims, wherein said formulation is provided as an ingredient in an energy bar or a nutritional bar.

18. The use of the formulation according to any one of the preceding claims for the preparation of a medicament for simultaneously stimulating and relaxing the central nervous system.

19. The use of the formulation according to any one of the preceding claims for the preparation of a medicament for enhancing energy in an individual.

20. The use of the formulation according to any one of the preceding claims for the preparation of a medicament for stimulating pleasure centers in the brain and body in an individual.

21. The use of the formulation according to any one of the preceding claims for the preparation of a medicament for suppressing the appetite in an individual.

22. The use of the formulation according to any one of the preceding claims for the preparation of a medicament for promoting both relaxation and mental alertness in an individual.

23. A formulation for down-regulating one or more stimulatory effects of green tea, comprising: mulungu, wherein said mulungu is provided in a dosage of about 150 mg to about 450 mg;

Bacopa monniera, wherein said Bacopa monniera is provided in a dosage of about 450 mg to about 900 mg; and

L-theanine, wherein said L-theanine is provided in a dosage of about 1 to 5 times the amount of caffeine in said green tea.

24. A formulation for down-regulating one or more stimulatory effects of caffeine, comprising: mulungu, wherein said mulungu is provided in a dosage of about 150 mg to about 450 mg;

L-theanine, wherein said L-theanine is provided in a dosage of about 1 to 5 times the amount of said caffeine.