COMPOSITIONS AND METHODS FOR PROMOTING CELLULAR METABOLIC FITNESS

Abstract

Provided are methods and compositions for promoting cellular metabolism and cellular repair in a tissue of a subject in need thereof. The composition includes at least one N-methyl-D-aspartate receptor (NMDAR) modulator to modulate metabolic activity in cells and at least one nuclear factor erythroid 2-related factor 2 (NRF2) modulator to modulate repair activity in cells. Optionally, the composition also includes at least one inactive component and at last one microbial modulator. The composition synergistically modulates a positive-feedback signal-amplification cycle comprising NMDAR and NRF2 in cells, which, in turn, promotes cellular metabolic fitness (CMF) in a tissue of a subject in need thereof.

Claims

1. A method of modulating cellular metabolism and cellular repair in a tissue of a subject in need thereof, the method comprising administering a composition comprising at least one N-methyl-D-aspartate receptor (NMDAR) modulator and at least one nuclear factor erythroid 2-related factor 2 (NRF2) modulator to the subject.

2. The method of claim 1, wherein each NMDAR modulator of the at least one NMDAR modulator is an NMDAR glycine site modulator, an NMDAR redox site modulator, an NMDAR glutamate site modulator, an NMDAR polyamine site modulator, an NMDAR ion site modulator, or an NMDAR allosteric site modulator.

3. The method of claim 2, wherein the at least one NMDAR modulator comprises the NMDAR glycine site modulator, and wherein the NMDAR glycine site modulator is present in an amount by total weight from about 0.01% to about 100% of a total weight of NMDAR modulator.

4. The method of claim 3, wherein the NMDAR glycine site modulator is selected from the group consisting of: glycine, serine, D-serine, trimethylglycine, betaine, dimethylglycine, methylglycine, sarcosine, taurine, and phenylalanine.

5. The method of claim 2, wherein the at least one NMDAR modulator comprises the NMDAR redox site modulator, and wherein the NMDAR redox site modulator is present in an amount by total weight from about 0.01% to about 100% of a total weight of NMDAR modulator.

6. The method of claim 5, wherein the NMDAR redox site modulator is selected from the group consisting of: cystine, N-acetylcysteine, pyrroloquinoline quinone, and methoxatin.

7. The method of claim 2, wherein the at least one NMDAR modulator is the NMDAR glutamate site modulator, and wherein the NMDAR glutamate site modulator is present in an amount by total weight from about 0.01% to about 100% of a total weight of NMDAR modulator.

8. The method of claim 7, wherein the NMDAR glutamate site modulator is selected from the group consisting of: glutamic acid, pyroglutamic acid, aspartic acid, D-aspartic acid, N-methyl-D-aspartic acid, alanine, and theanine.

9. The method of claim 2, wherein the at least one NMDAR modulator is the NMDAR polyamine site modulator, and wherein the NMDAR polyamine site modulator is present in an amount by total weight from about 0.005% to about 50% of a total weight of NMDAR modulator.

10. The method of claim 9, wherein the NMDAR polyamine site modulator is selected from the group consisting of: spermine, spermidine, and agmatine.

11. The method of claim 2, wherein the at least one NMDAR modulator is the NMDAR ion site modulator, and wherein the NMDAR ion site modulator is present in an amount by total weight from about 0.005% to about 50% of a total weight of NMDAR modulator.

12. The method of claim 11, wherein the NMDAR ion site modulator is selected from the group consisting of: magnesium, calcium, and potassium.

13. The method of claim 2, wherein the at least one NMDAR modulator is the NMDAR allosteric site modulator, and wherein the NMDAR allosteric site modulator is present in an amount by total weight from about 0.005% to about 50% of a total weight of NMDAR modulator.

14. The method of claim 13, wherein the NMDAR allosteric site modulator is selected from the group consisting of: dehydroepiandrosterone sulfate (DHEA-S) and pregnenolone sulfate (PREGS).

15. The method of claim 1, wherein each NRF2 modulator of the at least one NRF2 modulator is present in an amount by total weight from about 0.005% to about 50% of a total weight of NMDAR modulator.

16. The method of claim 15, wherein each NRF2 modulator of the at least one NRF2 modulator is selected from the group consisting of: lipoic acid, thioctic acid, R-lipoic acid, niacin, nicotinic acid, beta-hydroxybutyric acid, and butyric acid.

17. The method of claim 1, wherein administering the composition to the subject comprises an enteral administration or a parenteral administration.

18. The method of claim 1, wherein the at least one NMDAR modulator is present in a range of about 99.5 wt. % to about 60 wt. %, and wherein the at least one NRF2 modulator is present in a range of about 0.5 wt. % to about 40 wt. %.

19. The method of claim 18, wherein the at least one NMDAR modulator is about 86 wt. %, and wherein the at least one NRF2 modulator is about 13 wt. %.

20. The method of claim 1, wherein the composition further comprises at least one inactive component, and wherein each inactive component of the at least one inactive component is selected from the group consisting of: hydroxypropylmethyl cellulose, cellulose gel, hydroxypropyl cellulose, magnesium stearate, erythritol, glycerin, wheat germ oil, wheat germ extract, xanthan gum, acacia gum, lavender essential oil, cedar wood essential oil, rosemary essential oil, and water.

21. The method of claim 1, wherein the composition further comprises at least one microbial modulator, and wherein the at least one microbial modulator is present in an amount by total weight from about 0.1% to about 1000% of the total weight of the NMDAR modulator.

22. The method of claim 21, wherein the at least one microbial modulator is selected from the group consisting of: boric acid, sorbic acid, preservative, anti-fungal, anti-bacterial, anti-microbial, anti-viral, probiotic, prebiotic, synbiotic, bacteriophage, phage, and plasmid.

23. A composition for modulating cellular metabolism and cellular repair in a tissue of a subject in need thereof, the composition comprising at least one N-methyl-D-aspartate receptor (NMDAR) modulator and at least one nuclear factor erythroid 2-related factor 2 (NRF2) modulator.

24. The composition of claim 23, further comprising at least one inactive component, wherein each inactive component of the at least one inactive component is selected from the group consisting of: polysaccharide, modified cellulose, magnesium stearate, sweetener, glycerin, vegetable oil, mineral oil, gum, emulsifier, essential oil, and water.

25. The composition of claim 23, further comprising at least one microbial modulator, and wherein the at least one microbial modulator is present in an amount by total weight from about 0.1% to about 1000% of the total weight of the NMDAR modulator.

26. The composition of claim 25, wherein each microbial modulator of the at least one microbial modulator is selected from the group consisting of: boric acid, sorbic acid, preservative, anti-fungal, anti-bacterial, anti-microbial, anti-viral, probiotic, prebiotic, synbiotic, bacteriophage, phage, and plasmid.

27. The composition of claim 23, wherein each of the at least one NMDAR modulator, the at least one NRF2 modulator, and the at least one microbial modulator is about 0.01% to about 10% of a total weight of the composition.

28. The composition of claim 23, wherein an administration of the composition to the subject in need thereof comprises an enteral administration, and wherein the enteral administration comprises an oral or a sublingual administration of a dose of the composition at least once daily.

29. The composition of claim 28, wherein the daily dose of the composition comprises about 0.01 grams to about 10 grams of each of the at least one NMDAR modulator and the at least one NRF2 modulator.

30. The composition of claim 23, wherein an administration of the composition to the subject in need thereof comprises a parenteral administration.

Description

EXAMPLES

[0338] The present invention is further illustrated by the following example compositions and methods. There are many disorders that can potentially be treated by embodiments of the invention. The following examples should not be construed in any way as to be imposing limitations on the invention. On the contrary, they should allow those skilled in the art to derive other embodiments from modifications and combinations of these examples without departing from the spirit of the present invention and the scope of the potential claims.

[0339] The following examples of the invention are commixtures demonstrating potent stimulation of cellular metabolic fitness (CMF). These commixtures are suitable for oral and topical administration.

1. Glutamic acid, glycine, cystine, lipoic acid
2. Pyroglutamic acid, trimethylglycine, N-acetylcysteine, lipoic acid
3. Glutamic acid, glycine, cystine, lipoic acid
4. Pyroglutamic acid, trimethylglycine, N-acetylcysteine, lipoic acid
5. Glycine, cystine, lipoic acid, sodium bicarbonate
6. Glycine, lipoic acid, sodium bicarbonate
7. Glycine, serine, lipoic acid
8. Serine, lipoic acid
9. D-serine, lipoic acid
10. D-aspartic acid, lipoic acid
11. Serine, caffeine, lipoic acid
12. Trimethylglycine, N-acetylcysteine, alpha-lipoic acid
13. Glutamic acid, glycine, cystine, calcium beta-hydroxybutyrate
14. Pyroglutamic acid, trimethylglycine, N-acetylcysteine, calcium beta-hydroxybutyrate
15. Glutamic acid, glycine, cystine, caffeine, lipoic acid
16. Pyroglutamic acid, trimethylglycine, N-acetylcysteine, caffeine, lipoic acid
17. D-aspartic acid, glycine, cystine, alpha-lipoic acid, caffeine, lipoic acid
18. Pyroglutamic acid, trimethylglycine, N-acetylcysteine, lipoic acid, caffeine
19. Glutamic acid, glycine, cystine, calcium lactate, lipoic acid, caffeine
20. Aspartic acid, trimethylglycine, cystine, calcium beta-hydroxybutyrate, lipoic acid, caffeine
21. Phenylalanine, theanine, agmatine, taurine, lipoic acid

Treatments for Metabolism and Repair

[0340] Orally administered dietary supplement compositions containing commixtures of CMF modulators could mitigate the loss of metabolic function and tissue repair. The following six examples of the invention have been discovered to demonstrate synergistic activation of CMF within the weight percent ranges listed below.

22. Dietary Supplement Active Ingredients

[0341]

TABLE-US-00001 Weight % 1.00-50.0% Glycine Weight % 1.00-60.0% Glutamic Acid Weight % 0.50-30.0% N-Acetylcysteine Weight % 0.50-20.0% Alpha-Lipoic Acid

23. Dietary Supplement Active Ingredients

[0342]

TABLE-US-00002 Weight % 1.00-50.0% Trimethylglycine Weight % 1.00-60.0% Glutamic Acid Weight % 0.50-30.0% N-Acetylcysteine Weight % 0.50-20.0% Alpha-Lipoic Acid

24. Dietary Supplement Active Ingredients

[0343]

TABLE-US-00003 Weight % 1.00-50.0% Glycine Weight % 1.00-50.0% Pyroglutamic Acid Weight % 0.50-40.0% N-Acetylcysteine Weight % 0.50-30.0% Alpha-Lipoic Acid

25. Dietary Supplement Active Ingredients

[0344]

TABLE-US-00004 Weight % 1.00-50.0% Trimethylglycine Weight % 1.00-50.0% Pyroglutamic Acid Weight % 0.50-40.0% N-Acetylcysteine Weight % 0.50-40.0% Alpha-Lipoic Acid

26. Dietary Supplement Active Ingredients

[0345]

TABLE-US-00005 Weight % 0.50-25.0% Glycine Weight % 0.50-25.0% Trimethylglycine Weight % 1.00-60.0% Glutamic Acid Weight % 0.50-30.0% N-Acetylcysteine Weight % 0.50-20.0% Alpha-Lipoic Acid

27. Dietary Supplement Active Ingredients

[0346]

TABLE-US-00006 Weight % 0.50-25.0% Glycine Weight % 0.50-25.0% Trimethylglycine Weight % 1.00-50.0% Pyroglutamic Acid Weight % 0.50-30.0% N-Acetylcysteine Weight % 0.50-20.0% Alpha-Lipoic Acid

[0347] The following list of inactive ingredients would be suitable to add to the previous six examples within the weight percent ranges listed to attain desirable physical properties for encapsulated oral supplements.

TABLE-US-00007 Weight % 0.25-50.0% Hydroxypropylmethyl Cellulose Weight % 0.20-40.0% Cellulose Gel Weight % 0.10-20.0% Hydroxypropyl Cellulose Weight % 0.10-20.0% Magnesium Stearate

[0348] The following example of a preferred embodiment of the invention has been discovered to demonstrate synergistic activation of CMF. The following contents are packaged as a size “OO” capsule. The recommended dosing is three capsules taken twice a day.

28. Dietary Supplement Active Ingredients

[0349]

TABLE-US-00008 Weight 250 mg Trimethylglycine Weight 250 mg Pyroglutamic Acid Weight 150 mg N-Acetylcysteine Weight 100 mg Alpha-Lipoic Acid Weight 15 mg Hydroxypropylmethyl Cellulose Weight 15 mg Cellulose Gel Weight 10 mg Hydroxypropyl Cellulose Weight 10 mg Magnesium Stearate

Treatments for SCALP

[0350] The age-related changes in the scalp could be treated with the routine topical application of leave-in conditioner or dry shampoo compositions containing a commixture of CMF modulators. The following list of CMF modulators have been discovered in said compositions to demonstrate synergistic activation of CMF within the weight percent ranges listed below.

29. Topical Treatment Active Ingredients

[0351]

TABLE-US-00009 Weight % 0.10-3.00% Glutamic Acid Weight % 0.05-1.50% Glycine Weight % 0.10-3.00% N-Acetylcysteine Weight % 0.13-4.00% Lipoic Acid Weight % 0.07-2.00% Calcium Chloride Weight % 0.27-8.00% Calcium Carbonate Weight % 0.04-1.20% Sodium Chloride Weight % 0.16-4.80% Potassium Chloride Weight % 0.03-1.00% Potassium Sorbate Weight % 0.13-4.00% Caffeine

[0352] The following list of inactive ingredients would be suitable to include in said compositions within the weight percent ranges listed to attain desirable physical properties for leave-in conditioners and dry shampoos.

TABLE-US-00010 Weight % 0.64-19.20%  Erythritol Weight % 0.40-12.00%  Glycerin Weight % 0.20-6.00% Wheat Germ Oil Weight % 0.17-5.00% Wheat Germ Extract Weight % 0.07-2.00% Xanthan Gum Weight % 0.08-2.40% Acacia Gum Weight % 0.03-1.00% Lavender Essential Oil Weight % 0.02-0.50% Cedarwood Essential Oil Weight % 0.02-0.50% Rosemary Essential Oil Weight % 97.22-16.50%  Water

[0353] These compositions require several months of application before significant improvements in the scalp are noticeable. Though, surprisingly, these compositions demonstrate instantaneous effects consistent with CMF activation. Within minutes of application, a warming sensation around the scalp is experienced and a generalized sense of increased mental energy, like from a caffeinated energy drink, is experienced.

30. Topical Treatment Active Ingredients

[0354]

TABLE-US-00011 Weight % 0.015-1.5%   Serine Weight % 0.015-1.5%   Cystine Weight % 0.02-2% Lipoic Acid Weight % 0.05-5% Glycine Weight % 0.1-10% Bicarbonate Weight % 0.02-2% Monk Fruit Weight % 0.04-4% Stevia Weight % 0.03-2% Xanthan Gum Weight % 0.05-1% Potassium Sorbate Weight % 0.2-20% Calcium Beta-hydroxybutyrate Weight % 0.2-10% Boric Acid Weight % 0.4-10% Urea Weight % .sup. 1-30% Vegetable Oil Weight % .sup. 3-40% Glycerin Weight %  10-80% Witch Hazel

31. Topical Treatment Active Ingredients

[0355]

TABLE-US-00012 Weight % 0.015-1.5%   Caffeine Weight % 0.015-1.5%   Cystine Weight % 0.02-2% Lipoic Acid Weight % 0.05-5% Glycine Weight % 0.1-10% Bicarbonate Weight % 0.02-2% Monk Fruit Weight % 0.04-4% Stevia Weight % 0.03-2% Xanthan Gum Weight % 0.05-1% Potassium Sorbate Weight % 0.2-20% Calcium Beta-hydroxybutyrate Weight % 0.2-10% Boric Acid Weight % 0.4-10% Urea Weight % .sup. 1-30% Vegetable Oil Weight % .sup. 3-40% Glycerin Weight %  10-80% Witch Hazel

[0356] In addition, an increased sensitivity to caffeinated beverages is experienced when using these compositions, leading the recommendation that people using compositions containing commixtures of CMF activators should reduce their caffeine consumption to avoid unpleasant caffeine side-effects.

[0357] While the invention has been described in detail with respect to specific embodiments thereof, it will be appreciated that those skilled in the art, upon attaining an understanding of the foregoing, may readily conceive of alterations to, variations of, and equivalents to these embodiments. Accordingly, the scope of the present invention should be assessed as that of the potential claims and any equivalents thereof. The foregoing has been described of certain non-limiting embodiments of the present disclosure. Those of ordinary skill in the art will appreciate that various changes and modifications to this description may be made without departing from the spirit or scope of the present disclosure, as defined in the following claims.