NUTRITIONAL SUPPLEMENT FOR INCREASING COGNITIVE FUNCTIONS

Abstract

The invention provides compositions and methods that are effective to improve NO production in vivo and/or to increase NO levels in blood. Such compositions and methods are useful to increase oxygenation of the brain and to improve cognitive function.

Claims

1-19. (canceled)

20. A method to increase NO levels in the blood of a mammal comprising administering two unit dosage forms a day to the mammal, wherein each unit dosage form comprises: L-citrulline 500 mg20 mg; L-arginine 250 mg20 mg; and at least about 5 mg piperine.

21. The method of claim 20 wherein each unit dosage form comprises at least about 5.5 mg piperine.

22. The method of claim 20 wherein each unit dosage form comprises at least about 480 mg of L-citrulline.

23. The method of claim 20 wherein each unit dosage form comprises at least about 230 mg of L-arginine.

24. The method of claim 20 wherein each unit dosage form further comprises microcrystalline cellulose, silicon dioxide, and magnesium sterate.

25. The method of claim 20 wherein each unit dosage form is formulated as a capsule, powder, or liquid.

26. A method to increase oxygenation of the brain in a mammal comprising administering two unit dosage forms a day to the mammal, wherein each unit dosage form comprises: L-citrulline 500 mg20 mg; L-arginine 250 mg20 mg; and at least about 5 mg piperine.

27. The method of claim 26 wherein each unit dosage form comprises at least about 5.5 mg piperine.

28. The method of claim 26 wherein each unit dosage form comprises at least about 480 mg of L-citrulline.

29. The method of claim 26 wherein each unit dosage form comprises at least about 230 mg of L-arginine.

30. The method of claim 26 wherein each unit dosage form further comprises microcrystalline cellulose, silicon dioxide, and magnesium sterate.

31. The method of claim 26 wherein each unit dosage form is formulated as a capsule, powder, or liquid.

32. A method to improve cognitive function in a mammal comprising administering two unit dosage forms a day to the mammal, wherein each unit dosage form comprises: L-citrulline 500 mg20 mg; L-arginine 250 mg20 mg; and at least about 5 mg piperine.

33. The method of claim 32 wherein each unit dosage form comprises at least about 5.5 mg piperine.

34. The method of claim 32 wherein each unit dosage form comprises at least about 480 mg of L-citrulline.

35. The method of claim 32 wherein each unit dosage form comprises at least about 230 mg of L-arginine.

36. The method of claim 32 wherein each unit dosage form further comprises microcrystalline cellulose, silicon dioxide, and magnesium sterate.

37. The method of claim 32 wherein each unit dosage form is formulated as a capsule, powder, or liquid.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0011] FIGS. 1 shows the conversion of L-citrulline and L-argenine to NO.

[0012] FIG. 2 shows how Nitric Oxide Synthase (NOS) in endothelial cells converts L-arginine to L-hydroxyarginine and subsequently to nitric oxide (NO) and L-citrulline.

[0013] FIG. 3 shows the structure for piperine.

DETAILED DESCRIPTION

[0014] As used herein, the term about has its generally accepted meaning. In one embodiment, the term about means10% of the associated value. For example, about 100 mg means 100 mg10 mg. In one embodiment, the term about means5% of the associated value. For example, about 100 mg means 100 mg5 mg. In one embodiment, the term about means2% of the associated value. For example, about 100 mg means 100 mg2 mg. In one embodiment, the term about means1% of the associated value. For example, about 100 mg means 100 mg1 mg.

[0015] In one embodiment a unit dosage form of the invention may contain one or more pharmaceutical diluents or excipients. For example, in one embodiment a unit dosage form of the invention may comprise microcrystalline cellulose, silicon dioxide, and magnesium stearate.

[0016] In one embodiment a unit dosage form of the invention may comprise at least about 480 mg of L-citrulline.

[0017] In one embodiment a unit dosage form of the invention may comprise at least about 490 mg of L-citrulline.

[0018] In one embodiment a unit dosage form of the invention may comprise at least about 500 mg of L-citrulline.

[0019] In one embodiment a unit dosage form of the invention may comprise at least about 230 mg of L-arginine.

[0020] In one embodiment a unit dosage form of the invention may comprise at least about 240 mg of L-arginine.

[0021] In one embodiment a unit dosage form of the invention may comprise at least about 250 mg of L-arginine.

[0022] In one embodiment the piperine is synthetically produced piperine.

[0023] In one embodiment the piperine is an extract from the fruit of Piper.

[0024] L-Argenine is an -amino acid that is used in the biosynthesis of proteins. It is the precursor for the biosynthesis of nitric oxide. L-Argenine has the following structure:

##STR00001##

In humans, arginine is classified as a semiessential or conditionally essential amino acid, depending on the developmental stage and health status of the individual. L-Argenine is commercially available from a variety of sources.

[0025] L-Citrulline is an a-amino acid that is a key intermediate in the urea cycle, the pathway by which mammals excrete ammonia by converting it into urea. Citrulline is also produced as a byproduct of the enzymatic production of nitric oxide from the amino acid arginine, catalyzed by nitric oxide synthase. L-Citrulline has the following structure:

##STR00002##

L-Citrulline is commercially available from a variety of sources.

[0026] Bioperine is a patented absorption enhancer, obtained from black pepper fruits (Piper nigrum). Bioperine helps the body absorb the amino acids (see U.S. Pat. No. 5,536,506 and European Patent EP0810868B1). Bioperine (extract) inhibits human CYP3A4 and P-glycoprotein enzymes. By inhibiting certain enzymes Bioperine (extract) may alter the effectiveness of certain medications by increasing bioavailability. Bioperine is Generally Recognized As Safe (GRAS). Bioperine (CAS Reg. No. 94-62-2) is named as 1-piperylpiperidine; 5-(1,3-benzodioxol-5-yl)-1-(piperidin-1-yl)penta-2,4-dien-1-one; and (2E,4E)-5-(1,3-benzodioxol-5-yl)-1-(piperidin-1-yl)penta-2,4-dien-1-one, and has the structure:

##STR00003##

1-Piperylpiperidine is commercially available from a variety of sources.

[0027] The invention will now be illustrated by the following non-limiting Examples.

EXAMPLE 1.

[0028] The chart below describes the changes between the old formulation and the present invention based on the satisfaction rate for the customer's processing fees. The new formulation shows a 19.9 percent increase processing speed over four months as opposed to the old formulation with only as 2.9 percent increase in processing speed.

TABLE-US-00001 Old Formulation Present Invention Satisfaction Rate Satisfaction Rate Baseline 688 59 At 4 Month 62.3 78.9 % Increase 2.9 19.9

[0029] All publications, patents, and patent documents are incorporated by reference herein, as though individually incorporated by reference. The invention has been described with reference to various specific and preferred embodiments and techniques. However, it should be understood that many variations and modifications may be made while remaining within the spirit and scope of the invention.