STABILISED HYPOCHLOROUS SOLUTIONS AND THEIR MEDICAL COSMETIC USES

Abstract

A stabilised hypochlorous solution is disclosed. The solution includes hypochlorous acid (HOCl), hypochlorite (ClO—), and chlorine (Cl—) that combine to provide a total chlorine concentration. The total chlorine concentration is at or below 300 ppm, the hypochlorous acid, measured by UV spectroscopy at 230 nm, is the predominant species, the hypochlorite, measured by UV spectroscopy at 290 nm, is present at significantly lower levels than that of the hypochlorous acid, such that a ratio of hypochlorous acid to hypochlorite is greater than 7.5:1. The solution has a pH of between about 7 and 4 and a shelf life of at least 12 months, at 22° C., such that the amount of hypochlorous present remains at above 80% of its starting concentration, and the pH remains above 4.

Claims

1. A stabilised hypochlorous solution contained in a bottle impervious to light, comprising: hypochlorous acid (HOCl), hypochlorite (ClO—), and chlorine (Cl—), which species combined provide a total chlorine concentration, wherein the stabilised hypochlorous solution is obtained by stoichiometric control of reactants water, calcium or sodium hypochlorite salt and phosphoric acid utilising: i) a source of de-ionised water having an electrical conductivity of no more than 50 μScm-1 at 20° C.; ii) a greater than 60% pure calcium or sodium hypochlorite salt; and iii) phosphoric acid, to adjust the pH to between 3.0 and 6.5; the total chlorine concentration is at or below 300 ppm; the hypochlorous acid, measured by UV spectroscopy at 230 nm, is the predominant species; the hypochlorite, measured by UV spectroscopy at 290 nm, is present at lower levels than that of the hypochlorous acid, such that a ratio of hypochlorous acid to hypochlorite is greater than 7.5:1, and the solution has a pH of between about 7 and 4 and a shelf life of at least 12 months, at 22° C., such that the amount of hypochlorous present remains at above 80% of its starting concentration, and the pH remains above 4.

2. A stabilised hypochlorous solution as claimed in claim 1, which has a once open life of at least 4 weeks, at 22° C., such that the amount of hypochlorous present remains at above 80% of its concentration before opening.

3. A stabilised hypochlorous solution as claimed in claim 1, wherein the ratio of hypochlorous acid to hypochlorite is greater than 9:1.

4. A stabilised hypochlorous solution as claimed in claim 1, wherein the total chlorine concentration is 250 ppm+/−20% and the starting concentration of the hypochlorous is between 120 and 160 ppm.

5. A stabilised hypochlorous solution as claimed in claim 1, wherein the total chlorine concentration is 80 ppm+/−20% and the starting concentration of the hypochlorous is above 40 ppm.

6. A stabilised hypochlorous solution as claimed in claim 1, for use in wound healing.

7. A stabilised hypochlorous solution as claimed in claim 6, wherein the wound is a chronic wound.

8. A stabilised hypochlorous solution as claimed in claim 7, wherein the chronic wound is an ulcer.

9. A stabilised hypochlorous solution as claimed in claim 7, wherein the wound is a burn.

10. A stabilised hypochlorous solution as claimed in claim 1, for use in the treatment of urticaria.

11. A stabilised hypochlorous solution as claimed in claim 1, for use in the treatment of acne, spots, pimples and the like.

12. A stabilised hypochlorous solution as claimed in claim 1, for use at least one of before, during and after tattooing.

13. A stabilised hypochlorous solution as claimed in claim 5, for use in dentistry.

14. A stabilised hypochlorous solution as claimed in claim 13, which is a mouthwash.

15. A stabilised hypochlorous solution as claimed in claim 1, which is packaged for delivery as a nebuliser or nasally.

16. A method of treating a subject for a condition selected from treatment of wounds, burns, the oral cavity, urticaria or acne, sports or pimples comprising: administering a contained stabilised hypochlorous solution from a bottle impervious to light to the subject, the contained stabilised hypochlorous solution including: hypochlorous acid (HOCl), hypochlorite (ClO—), and chlorine (Cl—), which species combined provide a total chlorine concentration, wherein the stabilised hypochlorous solution is obtained by stoichiometric control of reactants water, calcium or sodium hypochlorite salt and phosphoric acid utilising: i) a source of de-ionised water having an electrical conductivity of no more than 500 μScm-1 at 20° C.; ii) a greater than 60% pure calcium or sodium hypochlorite salt; and iii) phosphoric acid, to adjust the pH to between 3.0 and 6.5; the total chlorine concentration is at or below 300 ppm; the hypochlorous acid, measured by UV spectroscopy at 230 nm, is the predominant species; the hypochlorite, measured by UV spectroscopy at 290 nm, is present at significantly lower levels than that of the hypochlorous acid, such that a ratio of hypochlorous acid to hypochlorite is greater than 7.5:1, and the solution has a pH of between about 7 and 4 and a shelf life of at least 12 months, at 22° C., such that the amount of hypochlorous present remains at above 80% of its starting concentration, and the pH remains above 4.

17. (canceled)

18. (canceled)

19. A method as claimed in claim 16, which has a once open life of at least 4 weeks, at 22° C., such that the amount of hypochlorous present remains at above 80% of its concentration before opening.

20. A method as claimed in claim 16, wherein the ratio of hypochlorous acid to hypochlorite is greater than 9:1.

21. A method as claimed in claim 16, wherein the total chlorine concentration is 250 ppm+/−20% and the starting concentration of the hypochlorous is between 120 and 160 ppm.

22. A method as claimed in claim 16, wherein the total chlorine concentration is 80 ppm+/−20% and the starting concentration of the hypochlorous is above 40 ppm.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0072] Embodiments of the invention are further described hereinafter with reference to the accompanying drawings, in which:

[0073] FIG. 1 is a graph showing the impact of microbial load on speed of healing;

[0074] FIG. 2 is an illustration of three microbial variables which impact on wound closure;

[0075] FIG. 3a is an illustration of the effect of two different concentrations of the hypochlorous solution of the invention on a range of microbes;

[0076] FIG. 3b illustrates the effect on viruses, including corona virus;

[0077] FIGS. 4a and 4b are graphs illustrating the significant difference in the hypochlorous: hypochlorite ratio of Applicant's stabilised hypochlorous solution, compared to a typical hypochlorous solutions of the art (produced by electrolysis and chemically stabilised) at an interval of 8 months;

[0078] FIG. 5 illustrates the effect of the hypochlorous solution (250 ppm) of the invention in healing burns;

[0079] FIG. 6 illustrates the effect of the hypochlorous solution (250 ppm) of the invention in healing ulcers;

[0080] FIG. 7 illustrates the effect of the hypochlorous solution of the invention (80 ppm) in oral hygiene;

[0081] FIG. 8 is a Table comparing the hypochlorous solution of the invention (at 250 ppm) with skin disinfectants of the art;

[0082] FIG. 9 illustrates the effect of the hypochlorous solution (250 ppm) of the invention in skin calming;

[0083] FIG. 10 illustrates the effect of the hypochlorous solution (250 ppm) of the invention on acne;

[0084] FIG. 11 shows the stability of the hypochlorous: hypochlorite ratio of the solution (250 ppm) of the invention over 24 months;

[0085] FIG. 12 shows the change in total chlorine concentration of the solution (250 ppm) of the invention at 22° C. over 4 weeks from opening;

[0086] FIG. 13 shows the change in total chlorine concentration of the solution (250 ppm) of the invention at 22° C. over 24 months;

[0087] FIG. 14 shows the change in pH of the solution (250 ppm) of the invention at 22° C. over 24 months;

[0088] FIGS. 15a and 15b are certificates of analysis for the solution (80 ppm) of the invention at time zero and 3 months, demonstrating retained stability;

[0089] FIG. 16 illustrates the difference in performance between the use of green soap applied pre and during tattooing and the hypochlorous solution (250 ppm) when applied pre, during and post tattooing; and

[0090] FIG. 17 illustrates the effects of the hypochlorous solution (250 ppm) over a 72-hour period having been applied pre, during and post tattooing

DETAILED DESCRIPTION

[0091] Referring to the figures, two formulations of the invention (about 250 ppm and about 80 ppm total chlorine) have been investigated in medicine. The term “about” is intended to provide for a +/−20% variation.

[0092] The first is a hypochlorous solution which has been tested in a range of settings including: piercing and aesthetics, as a skin cleanser, and then at a total chlorine concentration of 250 ppm (hypochlorous concentration of about 150 ppm) as a wound healing treatment in a range of conditions including: burns, ulcers, for the treatment of urticaria and in the treatment of acne, spots and pimples which may be medical or cosmetic in nature.

[0093] The second is a hypochlorous solution at a lower total chlorine concentration, 80 ppm (hypochlorous concentration of about 55 ppm), where it has been tested in a range of dentistry situations ranging from extractions, implants, dental caries, post treatment care, ulcers, mucosal bleeding, periodontis, lichen planus, implantis, gingivitis and poor oral hygiene, were it has been benchmarked against typical standard of care alternatives such as chlorhexidine gluconate.

[0094] FIG. 1 illustrates that the speed at which a wound heals is proportional to microbial load. Therefore, before conducting a procedure, such as, ear piercing or an aesthetic procedure, it is good practice to clean the skin to reduce microbial load.

[0095] In fact, as illustrated in FIG. 2a, the success of healing post incision changes dramatically with the log count of microbes, with the colony forming unit (CFU) figure of 10.sup.5 per ml or g being the tipping point between the chance of 90% closure (below) or 20% closure success (above).

[0096] Other significant factors include the diversity of microorganisms, and the presence or absence of, particularly, streptococcus. Thus, an active with wide ranging microbial action is desirable and FIGS. 3A and 3B illustrate the fact that the hypochlorous solution of the invention at 250 ppm reduced the count of a wide range of organisms by over 99.9%, and in fact over 99.99% or more, with a contact time of as little as 15 seconds.

[0097] Perhaps more surprisingly, even at 80 ppm a 99.99% reduction was achieved against 14 of the 15 organisms tested in FIG. 3a

[0098] FIG. 3b is a modified vaccina virus Ankara test report conducted according to EN 14476:2013+A1:2015. Again, it demonstrates a 4 log.sub.10 reduction in viral activity (greater than 99.99% inactivation) for the viruses identified on a 15 second exposure. Enveloped viruses are identified in bold.

[0099] These remarkable figures come down to the high initial concentration of hypochlorous relative to hypochlorite (FIG. 4a), (greater than 3:1) and the stability of the hypochlorous over time (FIG. 4b). Both FIGS. 4a and 4b provide a UV spectroscopy analysis of the relative concentration of hypochlorous and hypochlorite in applicant's product compared to a conventional hypochlorous solution. Its will be apparent from FIG. 4a that the ratio of hypochlorous to hypochlorite is very approximately 150:15 (10:1) for the (250 ppm) solution of the invention compared to very approximately 80:65 (1.25:1) for the comparator. This is highly significant because hypochlorous acid (HOCl) is 80-100 times more effective as an antimicrobial than hypochlorite (OCl.sup.−). More significantly both the ratio of hypochlorous to hypochlorite and the amounts are maintained over approx. 9 months.

[0100] The challenge is perhaps well illustrated by Table 1 below, which illustrates how bleach disassociates with pH.

TABLE-US-00001 TABLE 1 Free Cl2 ppm pH % HOCl % OCl  100 7.83 30% 70%  200 8.33 10% 90%  500 8.73  5% 95% 1000 9.24  3% 97% 2000 9.57  2% 98%
In other words, as pH increases so the relative proportions of hypochlorous decrease.

[0101] Applicants product is differentiated from products produced by e.g. electrolysis or less well stabilised chemistry based on the unprecedented high proportion of hypochlorous to hypochlorite and an initial pH of between 5 and 7. They demonstrate high efficacy at what would be considered relatively low doses of total chlorine, less than 500 ppm.

[0102] The beneficial effects of treatment with these solutions is illustrated in Examples 1 to 7 which utilise, respectively, solutions manufactured in accordance with the methodology of GB2521810 but producing much lower concentrations of total chlorine by careful control of the reactants: water, hypochlorite salt (typically the calcium or sodium salt), and acid. This results in a relatively low total chlorine content (below 500 ppm) but a high, predominant, concentration of hypochlorous, and a ratio of hypochlorous to hypochlorite of greater than 3:1 and often much higher (dependent on total chlorine concentration.)

[0103] A high purity hypochlorite salt, typically calcium or sodium, is stoichiometrically reacted with water having an electrical conductivity of no more than 500 μScm-1 at 20° C., and a pH controlling agent, typically phosphoric acid, and any phosphate precipitate (sodium or calcium phosphate) is removed by filtration. The initial pH is adjusted to be about pH 7.

Example 1

[0104] A patient with a burn wound, from a deep fat fryer, was treated with a 250 ppm stabilised hypochlorous solution of the invention following blister bursting. The solution was applied 3 times daily. The wound was fully healed at day 9. The results are illustrated in FIG. 5.

Example 2

[0105] A patient with what is termed a “chronic wound”, a non-healing ulcer, was treated with a 250 ppm stabilised hypochlorous solution, by its application onto a dressing, which was applied 3 times a day. The ulcer was fully healed at day 10. The results are illustrated in FIG. 6.

Example 3

[0106] A patient with a sore persisting bleeding mucosa (treated with steroids) was given a mouthwash comprising an 80 ppm stabilised hypochlorous solution of the invention. They gargled with it once per day for 2 weeks. The results are illustrated in FIG. 7.

[0107] That such a low concentration (total chlorine) dose is highly effective was surprising and compares highly favourably to traditional standards of care medications used in the dental industry as illustrated in FIG. 8, which in contrast to Example 3, was conducted with a 250 ppm hypochlorous solution.

Example 4

[0108] A patient who had fallen from a ladder into a bed of stinging nettles was treated with 250 ppm stabilised hypochlorous solution of the invention. 20 minutes post treatment the inflammation has significantly reduced as illustrated in FIG. 9 and the stinging ceased.

Example 5

[0109] A patient presenting with acne used the 250 ppm stabilised hypochlorous solution of the invention daily for 5 days and the improvement is illustrated in FIG. 10.

[0110] From the clinical Examples, and comparative data, it will be apparent that the solutions of the invention are acting in a highly effective manner.

[0111] The stability of the respective formulations is illustrated in FIGS. 11 to 15.

[0112] FIG. 11 shows the stability of the hypochlorous: hypochlorite ratio of the solution (250 ppm) of the invention generally remains constant with the hypochlorous level remaining between 120 and 160 ppm over 24 months, with the much lower hypochlorite levels also remaining constant.

[0113] FIG. 12 shows that even after opening the solution retains its total chlorine levels over a 4 weeks period.

[0114] FIG. 13 shows the change in total chlorine concentration of the solution (250 ppm) of the invention at 22° C. over 24 months. Over 6 months the total concentration remains at about 90% of the starting level, staying at over 80% for 12 months and over about 70% for up to 24 months.

[0115] FIG. 14 shows the change in pH of the solution (250 ppm) of the invention at 22° C. over 24 months. It stays above 5 for 6 months and above 4 over 24 months.

[0116] Finally, FIGS. 15a and 15b are certificates of analysis of the about 80 ppm solution of the invention at bottling and 3 months later. The striking feature of note is that the hypochlorous levels remain constant (greater than 90%) over time.

Example 6

[0117] A subject having tattoos applied to their left and right arms were treated with respectively, “green soap” on the left arm and a hypochlorous solution (250 ppm) of the invention on the right arm. The skin was wiped pre commencement of tattooing and during the tattooing process with the respective solutions. Post the tattooing the hypochlorous solution was applied 3 times a day. The results (tattoo appearance) are illustrated in FIG. 16 together with the bulleted findings. The use of the hypochlorous proved beneficial in a number of significant ways which also included a higher quality tattoo (better colouring and definition),

Example 7

[0118] A subject having a tattoo was followed and photographed immediately post having a tattoo applied and was followed and photographed at regular intervals over a 72-hour period. The results are illustrated in FIG. 17. All the benefits identified in Example 6 were experienced in this Example too.