Nitrite formulations and their use as nitric oxide prodrugs

• US 8,303,995 B1
• Filed: 08/16/2010
• Issued: 11/06/2012
• Est. Priority Date: 06/13/2008
• Status: Active Grant

• Current Assignee: Human Power Of N Company, Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Neogenis Laboratories, Inc., Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Bryan, Nathan Scott, Zand, Janet
• Primary Examiner(s): ARNOLD, ERNST V
• Application Number:
  US12/856,957
• Time in Patent Office: 813 Days
• Field of Search: None
• US Class Current: 424/718
• CPC Class Codes: A23K 50/50 for rodents
• CPC Class Codes: A23L 33/105 Plant extracts, their artificial duplicates or their derivatives
• CPC Class Codes: A23L 33/15 Vitamins
• CPC Class Codes: A23L 33/16 Inorganic salts, minerals or trace elements
• CPC Class Codes: A23L 33/175 Amino acids
• CPC Class Codes: A23V 2002/00 Food compositions, function of food ingredients or processes for food or foodstuffs
• CPC Class Codes: A23V 2200/326 having effect on cardiovascular health
• CPC Class Codes: A23V 2250/0606 Arginine
• CPC Class Codes: A23V 2250/156 Mineral combination undefined extract A23V2250/1638
• CPC Class Codes: A23V 2250/21 Plant extracts
• CPC Class Codes: A23V 2250/708 Vitamin C
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/375 Ascorbic acid, i.e. vitamin C; Salts thereof
• CPC Class Codes: A61K 31/714 Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
• CPC Class Codes: A61K 33/00 Medicinal preparations containing inorganic active ingredients
• CPC Class Codes: A61K 36/00 Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines antigens from pollen A61K39/36
• CPC Class Codes: A61K 36/21 Amaranthaceae (Amaranth family), e.g. pigweed, rockwort or globe amaranth
• CPC Class Codes: A61K 36/734 Crataegus (hawthorn)
• CPC Class Codes: A61K 45/06 : Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0056 : Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/0095 : Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006

Abstract

Compositions comprising from about 40 weight parts to about 1000 weight parts of a botanical nitrate source; from about 20 weight parts to about 500 weight parts of a botanical source of nitrite reduction activity; and from about 4 weight parts to about 100 weight parts of a nitrite salt. Methods of reducing triglycerides or reducing C-reactive protein levels are also provided.

Claims

1. A composition, comprising:

from about 40 weight parts to about 1000 weight parts of a botanical nitrate source;

from about 20 weight parts to about 500 weight parts of a botanical source of nitrite reduction activity; and

from about 4 weight parts to about 100 weight parts of a nitrite salt.

2. The composition of claim 1, wherein the botanical nitrate source is selected from the group consisting of beet root, artichoke, holy basil, gymnema sylvestre, ashwagandha root, salvia, St. John wort, broccoli, stevia, spinach, gingko, kelp, tribulus, eleuthero, epimedium, eucommia, hawthorn berry, rhodiola, green tea, codonopsys, panax ginseng, astragalus, pine bark, dodder seed, Schisandra, cordyceps, and mixtures thereof.

3. The composition of claim 1, wherein the botanical source of nitrite reduction activity is selected from the group consisting of hawthorn berry, Schisandra, green tea, beet root, pine bark, holy basil, gymnema sylvestre, ashwagandha root, salvia, St. John wort, broccoli, stevia, spinach, gingko, kelp, tribulus, eleuthero, epimedium, eucommia, rhodiola, green tea, codonopsys, panax ginseng, astragalus, dodder seed, cordyceps, berries, tea, beer, grapes, wine, olive oil, chocolate, cocoa, coffee, walnuts, peanuts, borojo, pomegranates, popcorn, yerba mate, and mixtures thereof.

4. The composition of claim 1, wherein the nitrite salt is selected from the group consisting of sodium nitrite, potassium nitrite, magnesium nitrite, calcium nitrite, and mixtures thereof.

5. The composition of claim 1, further comprising from about 20 weight parts to about 500 weight parts L-citrulline.

6. The composition of claim 1, further comprising from about 0.2 weight 5 parts to about 5 weight parts vitamin B12.

7. The composition of claim 6, wherein the vitamin B12 is in a form selected from the group consisting of methylcobalamin, cyanocobalamin, and mixtures thereof.

8. The composition of claim 1, further comprising from about 20 weight parts to about 500 weight parts vitamin C.

9. The composition of claim 8, wherein the vitamin C is in a form selected from the group consisting of magnesium ascorbate, sodium ascorbate, potassium ascorbate, ascorbic acid, and mixtures thereof.

10. The composition of claim 1, further comprising from about 50 weight parts to about 1500 weight parts of one or more other ingredients selected from the group consisting of mannitol, xylitol, sorbitol, sugar alcohols, cellulose, cellulose esters, cellulose ethers, modified celluloses, starch, modified starches, polysaccharides, oligosaccharides, disaccharides, saccharides, gelatin, polyvinylpyrrolidone, polyethylene glycol, binders, flavorants, colorants, magnesium stearate, antiadherent agents, stearate salts, sweeteners, silica, and lubricants.

11. The composition of claim 10, wherein:

the botanical nitrate source is selected from the group consisting of beet root, artichoke, holy basil, gingko, and mixtures thereof and is present at about 200 weight parts;

the botanical source of nitrite reduction activity is selected from the group consisting of hawthorn berry, Schisandra, green tea, beet root, pine bark, and mixtures thereof and is present at about 100 weight parts; and

the nitrite salt is selected from the group consisting of sodium nitrite, potassium nitrite, and mixtures thereof and is present at about 20 weight parts; and

the composition further comprises;

about 100 weight parts L-citrulline;

about 1 weight part vitamin B12 in a form selected from the group consisting of methylcobalamin, cyanocobalamin, and mixtures thereof; and

about 100 weight parts vitamin C in a form selected from the group consisting of magnesium ascorbate, ascorbic acid, and mixtures thereof.

12. The composition of claim 1, further comprising from about 20 weight parts to about 1000 weight parts L-arginine.

13. The composition of claim 1, further comprising from about from about 20 weight parts to about 500 weight parts of a nitrate salt selected from the group consisting of sodium nitrate, potassium nitrate, and mixtures thereof.

14. The composition of claim 1, wherein the composition is in a form of a lozenge dissolvable in the mouth.

15. The composition of claim 14, wherein the lozenge weighs from about 600 mg to about 2000 mg.

16. The composition of claim 11, wherein the composition is in a form of a lozenge dissolvable in the mouth.

17. The composition of claim 16, wherein the lozenge weighs from about 600 mg to about 2000 mg.