Systems and methods for topical treatment with nitric oxide

• US 6,103,275 A
• Filed: 06/10/1998
• Issued: 08/15/2000
• Est. Priority Date: 06/10/1998
• Status: Expired due to Term

• Current Assignee: Nitric Solutions Inc
• Original Assignee: Nitric Oxide Solutions
• Inventors: Balaban, Alexandru T., Seitz, William A., Stewart, Randall J., Garfield, Robert E.
• Primary Examiner(s): Reamer, James H.
• Application Number:
  US09/095,174
• Time in Patent Office: 797 Days
• Field of Search: 424/718
• US Class Current: 424/718
• CPC Class Codes: A61K 33/00 Medicinal preparations containing inorganic active ingredients
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00

Abstract

A simple, biocompatible system and procedure for generating nitric oxide (NO) is described. A mixture of powdered sodium nitrite, ascorbic acid, and maleic acid (or another organic acid of adequate strength) immediately generates nitric oxide (NO) on treatment with water. To slow down the NO generation, one may prepare an ointment from a nonaqueous medium (petrolatum, vaseline) and the three powdered ingredients, which on being applied topically on the skin will release NO as water permeates through this medium; alternatively, one may convert the aqueous sodium nitrite solution into a gel with hydroxyethylcellulose (or other gel-forming compound) and combine this gel with another gel obtained from aqueous ascorbic and maleic acids with hydroxyethylcellulose for topical application (on intact skin, burns, intra-cavity, etc.). The two gels may be admixed immediately before use (possibly from a single container with separate chambers and dual nozzle, via pushing or squeezing the two gels through the nozzle), or may be applied in sandwich-like fashion (possibly as a transdermal patch) for further slowing down the delivery of NO.

Claims

1. A method for therapeutically applying NO, the method comprising topically applying first gel comprising a nitrite salt, and a biocompatible reductant and a second gel comprising an acid with a pKa between about 1 and about 4 to a body site in an amount effective to enhance local blood flow.

3. The method of claim 1 or 2 where the reductant is an ascorbate salt, an erythrobate or α

-tocopherol.

4. The method of claim 1 or 2 where the reductant is ascorbic acid.

5. The method of claim 1 or 2 where thewhere the acid is an organic acid.

6. The method of claim 1 or 2 where the acid is maleic acid.

7. The method of claim 1 or 2 where the acid is an inorganic acid.

8. The method of claim 1 or 2 where the nitrite salt is an inorganic salt.

9. The method of claim 1 or 2 where the nitrite salt is sodium nitrite.

10. The method of claim 1 or 2 where the gels are aqueous gels.

11. The method of claim 1 or 2 where the body site is a burn.

2. A method for topical delivery of nitric oxide (NO) comprising applying an effective amount of a first gel comprising a nitrite salt, and a second gel comprising a biocompatible reductant, and an acid having a pKa between about 1 and about 4 to a body site.

12. A composition for generating and controlling the release rate of NO for topical applications, the composition comprising a first aqueous gel and a second aqueous gel, the first gel comprising a nitrite salt, and the second gel comprising an acid having a pKa between about 1 and about 4 and at least one of the first and second gel comprising biocompatible reductant.

13. The composition of claim 12 where the reductant is ascorbic acid, an ascorbate salt, an erythrobate or α

-tocopherol.

14. The composition of claim 12 where the reductant is ascorbic acid.

15. The composition of claim 12 where the acid is an organic acid.

16. The composition of claim 12 where the acid is maleic acid.

17. The composition of claim 12 where the acid is an inorganic acid.

18. The composition of claim 12 where the nitrite salt is an inorganic salt.

19. The composition of claim 12 where the nitrite salt is sodium nitrite.