METHOD OF PRODUCING PHYSIOLOGICAL AND THERAPEUTIC LEVELS OF NITRIC OXIDE THROUGH AN ORAL DELIVERY SYSTEM

• US 20160287628A1
• Filed: 01/06/2016
• Published: 10/06/2016
• Est. Priority Date: 06/15/2009
• 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: Joseph M. Maraia, Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Bryan, Nathan S., Rocca, Jose G.
• Granted Patent: US 9,821,006 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• 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 36/21 Amaranthaceae (Amaranth family), e.g. pigweed, rockwort or globe amaranth
• CPC Class Codes: A61K 36/734 Crataegus (hawthorn)
• CPC Class Codes: A61K 38/44 Oxidoreductases (1)
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• 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 9/20 Pills, tablets, discs, rods A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C12Y 107/02001 Nitrite reductase (NO-forming) (1.7.2.1)

Abstract

A composition and method of providing nitric oxide and nitrite therapy to patients whereby a therapeutic amount is bioavailable within approximately 30 minutes of administration. In embodiments of the invention, nitric oxide is produced in the oral cavity.

Claims

1. A delivery system comprising:

at least one nitric oxide-producing component; and

a dispersable medium adapted to be consumed in the oral cavity;

wherein the nitric oxide-producing component is adapted to generate nitric oxide in vivo upon consumption of the dispersable medium.

2. The delivery system of claim 1, wherein the dispersable medium is dissolvable in the oral cavity.

3. The delivery system of claim 1, wherein the dispersable medium is dissolvable in about five minutes or less.

4. The delivery system of claim 1, wherein the delivery system is adapted to generate nitric oxide in the oral cavity.

5. The delivery system of claim 1, where the nitric oxide-producing component is adapted to generate nitric oxide in-vivo in response to dissolution of the delivery system in the gastro intestinal tract.

6. The delivery system of claim 1, wherein the delivery system is formed of a lozenge, liquid, powder, solid, semi-solid, cream, gel, emulsion, suspension, heterogenic liquid, film, or topical.

7. The delivery system of claim 1, wherein the dispersable medium comprises one or more of a sugar, dispersing agent, flavor, sweetener, color, alcohol, maltodextren, or filler.

8. The delivery system of claim 1, wherein the nitric oxide-producing component is comprised of a nitrite, nitrate, or reductase or a combination of nitrite, nitrate and reductase.

9. The delivery system of claim 1 further comprising a barrier for preventing contact of two or more species of the nitric oxide-producing component.

10. The composition of claim 9, wherein the two or more species are nitrite and nitrite reductase.

11. The composition of claim 9, wherein the barrier is formed of a sugar, dispersing agent, flavors, sweetener, color, alcohol, maltodextren, or filler.

12. The composition of claim 1 further comprising a disintegrating agent, a compactible excipient, or both.

13. The composition of claim 12, wherein the disintegrating agent absorbs fluid upon contact with fluid.

14. The composition of claim 12, wherein the compactable excipient is adapted to maintain the delivery system in a compressed form.

15. The composition of claim 12, wherein the compactable excipient is chemically inert, does not absorb fluid, is non-hydroscopic, protects water-sensitive nitric oxide-producing components, does not react with nitric oxide-producing components and/or has a narrow particle size distribution.

16. The composition of claim 12 wherein the disintegrating agent causes the compactable excipient to break apart upon expansion.

26. A method of increasing levels of nitric oxide in an individual, comprising the step of orally delivering a therapeutically effective amount of a composition of claim 1 to the individual.

27. The method of claim 26, wherein the individual has endothelial dysfunction.

28. The method of claim 26, wherein the individual has hyperlipidemia, diabetes, hypertension, atherosclerosis and/or is a smoker.

29. A method of enhancing cardiovascular performance in an individual, comprising the step of orally administering a composition of claim 1 to the individual.

17. A composition comprising:

a nitrite;

reductase for said nitrite; and

a carrier for administration of said nitrite and said reductase to the buccal cavity.

18. The composition of claim 17, wherein the carrier is adapted to cause said nitrite to react with the reductase for said nitrite upon administration to the buccal cavity.

19. The composition of claim 17, wherein the carrier is adapted to maintain physical separation of the nitrite and the reductase for said nitrite prior to administration.

20. The composition of claim 17, where the composition is a lozenge liquid, powder, solid, semi-solid, cream, gel, emulsion, suspension, heterogenic liquid, film, or topical.

21. The composition of claim 17, wherein the carrier is of an amount sufficient to prevent contact of said nitrite and said nitrite reductase in a package.

23. The composition of claim 19, wherein the carrier has less than or equal to 50% particle size difference from nitrite.

24. The composition of claim 19, wherein the carrier has a particle size ranging from 50 to 500 microns.

25. The composition of claim 17, further comprising ascorbic acid and/or at least one polyphenol.

22. The composition of 17, wherein the nitrite is formed of a salt, is from a plant, is from a natural product, and/or is from cultured vegetable extract.