Physiologically balanced, ionized, acidic solution and methodology for use in wound healing

• US 20040137078A1
• Filed: 09/03/2003
• Published: 07/15/2004
• Est. Priority Date: 01/12/2000
• Status: Active Grant

• Current Assignee: NovaBay Pharmaceuticals, Inc.
• Original Assignee: NovaBay Pharmaceuticals, Inc.
• Inventors: Wang, Lu, Najafi, Ramin, Bassiri, Mansour, Yang, Jane
• Granted Patent: US 7,393,522 B2
• Time in Patent Office: Days
• US Class Current: 424/661
• CPC Class Codes: A01N 2300/00 Combinations or mixtures of active ingredients covered by classes A01N27/00 - A01N65/48 with other active or formulation relevant ingredients, e.g. specific carrier materials or surfactants, covered by classes A01N25/00 - A01N65/48
• CPC Class Codes: A01N 59/00 Biocides, pest repellants or attractants, or plant growth regulators containing elements or inorganic compounds
• 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 31/74 Synthetic polymeric materials
• CPC Class Codes: A61K 33/14 Alkali metal chlorides; Alkaline earth metal chlorides
• CPC Class Codes: A61K 33/24 Heavy metals; Compounds thereof
• CPC Class Codes: A61K 33/30 Zinc; Compounds thereof
• CPC Class Codes: A61K 33/40 Peroxides
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61L 2/0035 Gamma radiation
• CPC Class Codes: A61L 2/0088 Liquid substances
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: C01B 11/04 Hypochlorous acid
• CPC Class Codes: C02F 1/4618 for producing "ionised" acidic or basic water
• CPC Class Codes: C02F 2001/46185 only anodic or acidic water, e.g. for oxidizing or sterilizing
• CPC Class Codes: C02F 2103/026 Treating water for medical or cosmetic purposes
• CPC Class Codes: C02F 2201/46115 Electrolytic cell with membranes or diaphragms
• CPC Class Codes: C02F 2201/4618 Supplying or removing reactants or electrolyte
• CPC Class Codes: C02F 2209/04 Oxidation reduction potential [ORP]
• CPC Class Codes: C02F 2209/06 pH
• CPC Class Codes: C02F 2303/04 : Disinfection

Abstract

Described herein is a physiologically-balanced, acidic solution. Typically the solution is prepared by a chemical reactions or by the electrolysis of a solution comprising a mixture of an inorganic salt to form a physiologically balanced solution. This invention also relates to methods for use of the solutions, including a specialized bandage which may be used in combination with the solutions, or optionally with other topically applied materials. A mixture of inorganic salts and, optionally minerals, is used in order to mimic the electrolyte concentration and mixture of body fluid in an isotonic state. The solution typically comprises of one halide salt of lithium, sodium, potassium, calcium, and other cations. Typically the halide is fluoride, chloride, bromide, or iodide, and most typically chloride. A typical electrolyzed solution of the present invention has a pH within the range of about 2 to about 5, an oxidation reduction potential within the range of about +600 mV to about +1200 mV, and hypohalous acid concentration in the range of about 10 ppm to about 200 ppm. The solution has bactericidal, fungicidal, and sporicidal properties. The composition of the invention is nontoxic and has antibacterial properties, and is useful in any application in which antimicrobial properties are desirable.

Claims

1. A stable aqueous physiologically balanced, ionized solution comprising:

(a) an acidic solution of hypohalous acid with a concentration from about 10 ppm to about 200 ppm;

(b) a halide comprising salt, from about 0.4 g/L to about 20.4 g/L, said solution having a pH range from about 3.0 to about 4.0, and

(c) said solution when stored in a chemically non-reactive container at room temperature over at least three months, the solution is characterized as having a reduced hypohalous acid concentration of between 1-95% as determined by UV-VIS or by iodometric titration.

2. The stable solution of claim 1, wherein the pH ranges from about 3.5 to about 4.0.

3. The stable solution of claim 1, wherein the pH is about 3.5.

4. The stable solution of claim 1, wherein said solution when stored in a chemically non-reactive container at room temperature over at least three months, the solution is characterized as having a reduced hypohalous acid concentration of between 0-5% as determined by UV-VIS or by iodometric titration.

5. The stable solution of claim 1, wherein said solution when stored in a chemically non-reactive container at room temperature over at least three months, the solution is characterized as having a reduced hypohalous acid concentration of between 5-15% as determined by UV-VIS or by iodometric titration.

6. The stable solution of claim 1, wherein the hypohalous acid comprises the active chlorine species HOCl, NaOCl, and Cl₂, and the pH of the solution is about 3.5.

7. The stable solution of claim 1, wherein the chemically non-reactive container is a gas-tight, sealed container is made from material that is non-permeable and resistant to oxidative degradation.

8. The stable solution of claim 7, wherein the chemically non-reactive container is a gas-tight, sealed container made from PFA or equivalent Teflon compositions.

9. The stable solution of claim 7, wherein the container is non-permeable to the species of the NVC-101 solution.

10. The solution of claim 1 further characterized as having an original oxidation reduction potential (ORP) at room temperature ranging from about +600 mV to about +1200 mV, and said ORP ranging from no less than about 90 to 97.5% of the original ORP after three months at room temperature.

11. The solution of claim 1, wherein the hypohalous acid is selected from the group consisting of HOBr, HOI, HOCl, and HOF.

12. The solution of claim 1, wherein the hypohalous acid concentration is from about 40 to about 190 ppm.

13. The solution of claim 1, wherein the halide comprising salt is a member selected from the group consisting of lithium, sodium, potassium, magnesium, zinc, cesium, rubidium, and barium halide.

14. The solution of claim 1, wherein the halide comprising salt is a single salt.

15. The solution of claim 1, wherein the hypohalous acid concentration of the solution is measured by iodometric titration or UV-VIS spectroscopy.

16. The solution of claim 1, wherein the chemically non-reactive container is designed for single use or single application packaging.

19. A method for the treatment of various medical conditions selected from the groups consisting of promoting wound healing, reduction of pathogens in open wounds, wound decontamination, ocular disinfection or decontamination, oral disinfection, antifungal therapy, ophthalmic applications, reduction of pathogens in pulmonary infections, reduction of pathogens in burns, lavage, reduction of infectious load in organs for transplantation, reduction of bacterial load in autologous or artificial tissue transplantation, oral disinfection antifungal therapy, treatment of biofilm for cystic fibrosis or other diseases that produces biofilms, treatment of viral infections, treatment of skin diseases, and tissue repair and regeneration, which method comprises using the solution of claim 1 by applying the solution to the site where treatment is required.

29. A method for the treatment of various medical conditions selected from the groups consisting of promoting wound healing, reduction of pathogens in open wounds, wound decontamination, ocular disinfection or decontamination, oral disinfection, antifungal therapy, ophthalmic applications, reduction of pathogens in pulmonary infections, reduction of pathogens in burns, lavage, reduction of infectious load in organs for transplantation, reduction of bacterial load in autologous or artificial tissue transplantation, oral disinfection antifungal therapy, treatment of biofilm for cystic fibrosis or other diseases that produces biofilms, treatment of viral infections, treatment of skin diseases, and tissue repair and regeneration, which method comprises using the solution of claim 1 by applying the solution to the site where treatment is required.

30. A process for the preparation of the solution of claim 1 or claim 17, wherein the solution is prepared by chemical methods, including chemical synthesis, mechanical methods such as by mixing, electrolysis or prepared in situ.

31. The process of claim 30, wherein the halide comprising salt solution is converted to an acidic solution by electrolysis.

32. The process of claim 30, wherein the pH of the solution is adjusted to about 3.5 to about 4.0.

33. The process of claim 30, wherein the solution is prepared by chemical synthesis comprising of the following reactions:

NaOCl+HCl→

HOCl+NaCl

wherein the concentration of NaOCl in solution is about 2.5 mmol/L and the concentration of HCl is about 7.4 mmol/L, the resulting solution is adjusted to a pH of about 3.5 to about 4.0, and the solution is allowed to reach equilibrium without agitation for at least 2 hours.

34. The process of claim 33, wherein the resulting solution is adjusted to a pH of about 3.5.

35. The process of claim 30, wherein the solution is prepared in situ by mixing chemicals to form the stable aqueous physiologically balanced, non-cytotoxic ionized solution at the site of the tissue in need of treatment.

36. A method of promoting wound healing, reduction of pathogens in open wounds, wound decontamination, ocular disinfection or decontamination, oral disinfection, antifungal therapy, ophthalmic applications, reduction of pathogens in pulmonary infections, reduction of pathogens in burns, lavage, reduction of infectious load in organs for transplantation, reduction of bacterial load in autologous or artificial tissue transplantation, oral disinfection antifungal therapy, treatment of biofilm for cystic fibrosis or other diseases that produces biofilms, treatment of viral infections, treatment of skin diseases, and tissue repair and regeneration, or a combination thereof, by treating a patient in need of such therapy with an effective amount of a stable, physiologically-balanced, acidic composition comprising an aqueous solution of claim 1.

37. The method of claim 36, comprising:

a) exposing area of damaged tissue;

b) applying the solution to dermal tissue;

c) irrigation of damaged tissue using the solution; and

d) cleaning or treating tissue using the solution.

17. A stable aqueous physiologically balanced, ionized solution comprising:

(a) an acidic solution of hypochlorous acid with a concentration, from about 10 ppm to about 200 ppm;

(b) a chloride comprising salt, from about 0.4 g/L to about 16 g/L, said solution having a pH range from about 3.5 to about 4.0, and

(c) said solution when being stored in a chemically non-reactive, single use container at room temperature over at least three months and having a reduced hypochlorous acid concentration of between 1-95% as determined by UV-VIS or by iodometric titration.

18. The stable solution of claim 17, wherein the container is a single use PFA lined container.

20. A method for the treatment of various medical conditions selected from the groups consisting of promoting wound healing, reduction of pathogens in open wounds, wound decontamination, ocular disinfection or decontamination, oral disinfection, antifungal therapy, ophthalmic applications, reduction of pathogens in pulmonary infections, reduction of pathogens in burns, lavage, reduction of infectious load in organs for transplantation, reduction of bacterial load in autologous or artificial tissue transplantation, oral disinfection antifungal therapy, treatment of biofilm for cystic fibrosis or other diseases that produces biofilms, treatment of viral infections, treatment of skin diseases, and tissue repair and regeneration, which method comprises using the solution of claim 17 by applying the solution to the site where treatment is required.

21. The solution of claim 17 further characterized as having an original oxidation reduction potential (ORP) at room temperature ranging from about +600 mV to about +1200 mV, and said ORP ranging from no less than about 90 to 97.5% of the original ORP after at least three months at room temperature.

22. The solution of claim 17, wherein the hypochlorous acid concentration is from about 40 to about 190 ppm.

23. The solution of claim 17, wherein the chloride comprising salt is a member selected from the group consisting of lithium, sodium, potassium, magnesium, zinc, cesium, rubidium, and barium chloride.

24. The solution of claim 17, wherein the chloride comprising salt is a single salt.

25. The solution of claim 17, wherein the pH ranges from about 3.5 to about 4.0.

26. The solution of claim 24, wherein the chloride comprising salt is sodium chloride.

27. The solution of claim 26, wherein the concentration of sodium chloride is from about 4 g/L to about 9 g/L, and the pH is about 3.5.

28. The solution of claim 26, wherein the molar ratio range of OCl⁻

over the sum of OCl⁻

and HOCl at 20°

C. is about 0 to about 0.26%.