US 2006021 1721A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0211721 A1 Roberts (43) Pub. Date: Sep. 21, 2006 (54) NUTRACEUTICAL FORMULATION OFA Publication Classification COGNITIVE ENHANCEMENT SYSTEM (51) Int. Cl. A6II 3L/SL (2006.01) A6II 3/473 (2006.01) (76) Inventor: Alan R. Roberts, Los Angeles, CA A6II 3 L/455 (2006.01) (US) A6II 3L/98 (2006.01) (52) U.S. Cl. ......................... 514/276; 514/295; 514/356; 514/561 Correspondence Address: (57) ABSTRACT ARENT FOX PLLC A nutraceutical composition and method of use thereof 1050 CONNECTICUT AVENUE, N.W. includes core ingredients, huperzine A, dimethylaminoetha SUTE 4OO nol (DMAE), thiamin, niacin, and pantothenic acid. The WASHINGTON, DC 20036 (US) core ingredients provide a synergistic effect to improve and Support cognitive function, such as learning, thinking, and judging and to promote alertness, awareness, attention and mental clarity. Combinations of additional ingredients, such (21) Appl. No.: 11/084,189 as Vinpocetine, acetyl-L-carnitine, L-pyroglutamic acid, pyridoxine, folic acid, Vitamin B2, phosphatidylserine, L-theanine, and rhodiola rosea can be added to the core ingredients to enhance the beneficial and Synergistic effects (22) Filed: Mar. 21, 2005 of the composition. US 2006/021 1721 A1 Sep. 21, 2006 NUTRACEUTICAL FORMULATION OF A 0007 Huperzine is known to have additional beneficial COGNITIVE ENHANCEMENT SYSTEM properties. For instance, huperzine is known to be a revers ible butyrylcholinesterase inhibitor. Also, huperzine has FIELD OF THE INVENTION demonstrated good penetration through the blood brain barrier, high oral bioavailability, and long durations of 0001. The present invention relates to a nutraceutical inhibitory action on acetylcholinesterase. Furthermore, formulation with cognitive Support compounds that promote huperzine is also believed to protect neurons from cell death enhanced cognitive performance. caused by toxic levels of glutamate. 0008 Another substance thought to improve cognitive BACKGROUND OF THE INVENTION function is 2-dimethylaminoethanol (DMAE), which is a 0002 Attempts to enhance cognitive performance in chemical known to be produced in the brain. Researchers individuals have a long history. However, nutraceutical have linked the nutraceutical properties of DMAE to the interventions have had limited Success. A substantial amount presence and activity of choline. Specifically, researchers of research in the area of cognitive enhancement has been have noted that DMAE is structurally similar to choline, conducted to determine the efficacy of natural nutraceutical which is a precursor to acetylcholine, and which is believed agents (commonly referred to as “nutraceuticals” or “dietary to be important to cognitive function, as previously Supplements'). Such as Ginkgo biloba and ginseng, among described. It is believed that DMAE stimulates the produc others. tion of choline. It is also believed that DMAE is correlated to slowing cell membrane degradation. 0003. The FDA has defined a dietary supplement to be a product (other than tobacco) that is intended to Supplement 0009. Thiamin (also known as vitamin B) is known to be the diet that bears or contains one or more of the following critical in the conversion of blood Sugar, i.e., glucose, into dietary ingredients: a vitamin, a mineral, an herb or other cellular energy and it has been implicated in neurotransmis botanical, an amino acid, a dietary Substance for use by man sion and nerve conduction. The metabolic activities of to Supplement the diet by increasing the total daily intake, or thiamin primarily affect the nerves, muscles and cardiovas a concentrate, metabolite, constituent, extract, or combina cular system. It is also known that thiamin is involved in the tions of these ingredients. See, FDA Center for Food Safety synthesis of acetylcholine. and Applied Nutrition. Dietary Supplement Health Educa 0010 Niacin (also known as vitamin B) functions meta tion Act of 1994. Dorland's Illustrated Medical Dictionary bolically as a component of two important coenzymes: (30 ed.) defines nutrient as “a food or other substance that nicotinamide adenine dinucleotide (NAD) and nicotinamide provides energy or building material for the Survival and adenine dinucleotide phosphate (NADP), which play an growth of a living organism.” Accordingly, as used herein, essential role in over 200 chemical reactions in the body, a “nutraceutical' is any Substance that provides physiologi including oxidation-reduction reactions, ATP synthetic path cal, medical or health benefits or protection. ways, and ADP-ribose transfer reactions. Niacin has been linked to enhancing brain choline concentrations. 0004 The research into the efficacy of nutraceuticals has investigated the degree to which nutraceuticals may have 0011 Moreover, pantothenic acid (also known as vitamin practical application in short- and long-term cognitive Bs) is generally converted to a sulfur-containing compound enhancement or cognitive activity (herein collectively called pantetheline, which is further converted to coenzyme referred to as “cognitive function'). The research that has A. Coenzyme A is linked to cellular metabolism through been conducted in this area has revealed some beneficial energy-yielding oxidation of glycolytic products and other qualities in certain substances. For example, through this metabolites through the mitochondrial tricarboxylic acid research, nutraceuticals, such as Ginkgo biloba and Bacopa cycle. Pantothenic acid is also critical to the synthesis of monnieri have been shown to improve cognitive function to essential molecules, such as fatty acids, membrane phos Some degree. pholipids, and some amino acids. 0012. Other compounds have also been studied, and have 0005. Other substances that have been studied in the been correlated with the activity of brain and spinal tissues same context are discussed below. and possibly cognitive function. For example, L-pyro 0006 Huperzine A (generally referred to herein as glutamic acid (PCA or PGA) is chemically related to pyro “huperzine'), in particular, is an alkaloid found in the herb glutamate, which is an amino acid normally present in large Huperzia serrata and is generally believed to improve amounts in human brain, cerebral spinal fluid and blood. cognitive function. While not wishing to be bound by this Additionally, acetyl-L-carnitine (ALC) is known to facilitate theory, the nutraceutical effect of huperzine may be linked to the production of energy from long chain fatty acids, and the presence and activity of acetylcholine, which is known acetyl-L-carnitine is considered to be a cognitive enhancing to be a neurotransmitter in the central and peripheral nervous nutrient because it increases the production and release of system that appears to be correlated to cognition and acetylcholine in the brain. Some research has shown that memory. In particular, the loss of acetylcholine function acetyl-L-carnitine acts as a neuroprotective agent, including appears to be a significant factor in several disorders of brain reversing hippocampal and prefrontal neuronal loss and function, including Alzheimer's disease, which is believed lipofuscin accumulation in animals and slowing the decline to be a condition where there is a relative shortage of in the production of nerve growth factor (NGF) and NGF acetylcholine. Researchers believe that huperzine is an ace receptors. Moreover, vinpocetine is believed to be a potent tylcholinesterase (AChE) inhibitor, blocking the breakdown vasodilator and has been commonly used in the treatment of of acetylcholine. By inhibiting the enzyme that breaks down cerebrovascular disorders. acetylcholine, more acetylcholine becomes available to 0013 Nutraceutical compositions, which have been stimulate neurons. believed to enhance cognitive function, have been produced US 2006/021 1721 A1 Sep. 21, 2006 and commercialized for many years. Many of these conven 0019. In one variation of the present invention, DMAE is tional nutraceutical compositions are known to use numer preferably administered as DMAE bitartrate at a dose ous vitamins, compounds, and herbs to provide cognitive greater than 100 to about 1500 mg/day of DMAE bitartrate. benefits to the user. These compositions are colloquially Huperzine is administered at a dose from about 0.01 to about referred to as "cocktails' because these compositions com 1 mg/day. Thiamin is administered in the amount from about bine an array of active ingredients in seemingly arbitrary 25 to about 125 mg/day. Niacin is administered in the dosages. Also, because of the arbitrary nature of the com amount from about 100 to about 300 mg/day. Pantothenic positions, the potential for synergistic effects between the acid is administered in an amount greater than 100 to about ingredients is unpredictable. For example, typically these 300 mg/day. compositions combine ingredients, such as vitamins, min 0020. In another variation, the composition is combined erals, and natural herbs, each of which is believed in folklore with nutraceutically acceptable carriers or excipients to or by conventional wisdom to support cognitive function. assist oral, dermal, or parenteral delivery. In one more However, as is often the case, the ingredients are unproven variation, the composition is delivered orally in a tablet in terms of actual effectiveness, and sometimes safety. and/or capsule. In yet another variation, the dosages of the 0014. The present state of the art includes nutraceutical